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1
The Asp116-His116 substitution in a novel HLA-B27 subtype influences the acceptance of the peptide C-terminal anchor
Dergi Makalesi

Dergi Makalesi
Kaynak :
Springer Link
Dergi:
Immunogenetics
Yazar(lar) :
Maria Teresa Fiorillo , Giulia Greco , Rosa Sorrentino
Konu :
Genetics, Immunology
Yıl :
1995
Maria Teresa Fiorillo
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Kaydet Alıntıla
DOI : 10.1007/bf00188430
Anahtar Kelimeler : Peptide
ISSN: 0093-7711 1432-1211
Sayı: 1
Cilt: 41
Sayfa: 38-39
2
The multifaceted nature of NLRP12
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
Journal of Leukocyte Biology
Yazar(lar) :
Sinem Tuncer , Maria Teresa Fiorillo , Rosa Sorrentino
Yıl :
2014
Maria Teresa Fiorillo
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Kaydet Alıntıla
NLRs are a class of cytoplasmic PRRs with various functions, ranging from pathogen/damage sensing to the modulation of inflammatory signaling and transcriptional control of MHC and related genes. In addition, some NLRs have been implicated in preimplantation and prenatal development. NLRP12 (also known as RNO, PYPAF7, and Monarch‐1), a member of the family containing an N‐terminal PYD, a NBD, and a C‐terminal LRR region, is one of the first described NLR proteins whose role remains controversial. The interest toward NLRP12 has been boosted by its recent involvement in colon cancer, as well as in the protection against some severe infections, such as that induced by Yersinia pestis, the causative agent of plague. As NLRP12 is mainly expressed by the immune cells, and its expression is down‐regulated in response to pathogen products and inflammatory cytokines, it has been predicted to play a role as a negative regulator of the inflammatory response. Herein, we present an overview of the NLR family and summarize recent insights on NLRP12 addressing its contribution to inflammatory signaling, host defense, and carcinogenesis.
DOI : 10.1189/jlb.3ru0514-265rr
ISSN: 0741-5400
Sayı: 6
Cilt: 96
Sayfa: 991-1000
3
HLA-B27 and antigen presentation: At the crossroads between immune defense and autoimmunity
Dergi Makalesi

Dergi Makalesi
Kaynak :
Science Direct
Dergi:
Molecular Immunology
Yayıncı:
Elsevier
Yazar(lar) :
Rosa Sorrentino , Rainer A. Böckmann , Maria Teresa Fiorillo
Yıl :
2014
Maria Teresa Fiorillo
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Kaydet Alıntıla
The HLA-B27 is historically studied as a susceptibility factor in spondyloarthropathies and, primarily, in ankylosing spondylitis (AS). Over the recent years however, it has been rediscovered as protective factor against some severe viral infections. This is due to the high capacity of virus-specific, HLA-B27-restricted CD8+ T cells for both intrinsic (i.e. polyfunctionality, high avidity, low sensitivity to Treg cell-mediated suppression) and extrinsic (i.e. rapid and efficient antigen processing and presentation) factors. It is tempting to speculate that these two aspects are not independent and that the association of B27 molecules to autoimmunity is the downside of this superior functional efficacy which, in given genetic backgrounds and environmental conditions, can support a chronic inflammation leading to spondyloarthropathies. Still, the pathogenic role of HLA-B27 molecules in AS is elusive. Here, we focus on the biology of HLA-B27 from the genetics to the biochemistry and to the structural/dynamical properties of B27:peptide complexes as obtained from atomistic molecular dynamics simulation. Overall, the results point at the antigen presentation as the key event in the disease pathogenesis. In particular, an extensive comparison of HLA-B*2705 and B*2709 molecules, that differ in a single amino acid (Asp116 to His116) and are differentially associated with AS, indicates that position 116 is crucial for shaping the entire peptide-presenting groove.
DOI : 10.1016/j.molimm.2013.06.017
Anahtar Kelimeler : HLA-B27, Ankylosing spondylitis, Autoimmunity, Antigen presentation, Micropolymorphism, Molecular dynamics simulation
ISSN: 0161-5890
Sayı: 1
Cilt: 57
Sayfa: 22-27
Sınıflandırma :
4
HLA-B27 and Ankylosing Spondylitis geographic distribution as the result of a genetic selection induced by malaria endemic? A review supporting the hypothesis
Dergi Makalesi

Dergi Makalesi
Kaynak :
Science Direct
Dergi:
Autoimmunity Reviews
Yayıncı:
Elsevier
Yazar(lar) :
Alessandro Mathieu , Alberto Cauli , Maria Teresa Fiorillo , Rosa Sorrentino
Yıl :
2008
Maria Teresa Fiorillo
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The geographic distribution of HLA-B27 shows a latitude-related gradient inverse to that of malaria endemic. An apparent exception occurs in New Guinea, a region where malaria is present, but where HLA-B27 frequency shows, however, an orographic gradient antithetic to that of malaria incidence. We therefore suggest that Plasmodium falciparum may have exerted a negative selection on this gene. This might be due to a higher susceptibility to severe forms of malaria, associated with HLA-B27 or other close gene(s). In addition, we suggest here that the same selective pressure that has contributed to reduce the HLA-B27 frequency in some regions has favoured the fixing of newly generated B27 subtypes included in more advantageous HLA haplotypes. In some cases, as for B⁎2709 in Sardinia and B⁎2706 in Southeast Asia, these haplotypes may harbour factors that protect from Ankylosing Spondylitis, an autoimmune disease strongly associated with HLA-B27, thus offering a novel, powerful tool to dissect disease pathogenesis, and to identify additional genetic factors of susceptibility.
DOI : 10.1016/j.autrev.2008.03.013
ISSN: 1568-9972
Sayı: 5
Cilt: 7
Sayfa: 398-403
Sınıflandırma :
5
An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes
Dergi Makalesi

Dergi Makalesi
Kaynak :
Springer Nature
Dergi:
Scientific Reports
Yayıncı:
Springer Science and Business Media LLC
Yazar(lar) :
Fabiana Paladini , Maria Teresa Fiorillo , Carolina Vitulano , Valentina Tedeschi , Matteo Piga , Alberto Cauli , Alessandro Mathieu , Rosa SorrentinoFabiana Paladini , Maria Teresa Fiorillo , Carolina Vitulano , Valentina Tedeschi , Matteo Piga , Alberto Cauli , Alessandro Mathieu , Rosa Sorrentino
Yıl :
2018
Maria Teresa Fiorillo Maria Teresa Fiorillo
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Kaydet Alıntıla
DOI : 10.1038/s41598-018-28799-8
ISSN: 2045-2322
Sayı: 1
Cilt: 8
6
HLA Class I or Class II and Disease Association: Catch the Difference If You Can
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
Frontiers in Immunology
Yazar(lar) :
Maria Teresa Fiorillo , Fabiana Paladini , Valentina Tedeschi , Rosa Sorrentino
Yıl :
2017
Maria Teresa Fiorillo
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Kaydet Alıntıla
DOI : 10.3389/fimmu.2017.01475
Anahtar Kelimeler : HLA class I, HLA class II, autoimmune disease, T cell receptor, self-reactivity
ISSN: 1664-3224
Cilt: 8
Sınıflandırma :
7
Expression of the murine interleukin 6 receptor in hepatoma cells: the intracytoplasmic domain is not required for interleukin 6 signal transduction
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
European Journal of Immunology
Yazar(lar) :
Maria Teresa Fiorillo , Carlo Toniatti , Jacques Van Snick , Gennaro Ciliberto
Konu :
Immunology, Immunology and Allergy
Yıl :
1992
Maria Teresa Fiorillo
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This paper reports on cDNA coding for the 80‐kDa murine IL 6 receptor (mIL 6R) that was cloned from a mouse liver cDNA library. Human hepatoma Hep3B cells transfected transiently or stably with an expression vector carrying the entire coding region for mIL6R become responsive to mouse IL 6 (mIL 6). We monitored response to the cytokine through the transcriptional activation of a co‐transfected IL 6‐inducible human C‐reactive protein (CRP) promoter; response to mIL 6 is lost upon treatment of the cells with increasing amounts of a monoclonal antibody to mIL 6R. mIL 6R mutants have been generated in the carboxy‐terminal portion of the molecule. Their functional analysis in hepatoma cells shows that the intracytoplasmic domain of the receptor is not absolutely essential to IL 6 signal transduction (i.e. CRP promoter activation), but that the last 40 amino acids contribute to maximal IL 6 response in these cells.
DOI : 10.1002/eji.1830220325
ISSN: 0014-2980
Sayı: 3
Cilt: 22
Sayfa: 799-804
8
Analysis of human/mouse interleukin-6 hybrid proteins: both amino and carboxy termini of human interleukin-6 are required forin vitro receptor binding
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
European Journal of Immunology
Yazar(lar) :
Maria Teresa Fiorillo , Andrea Cabibbo , Paola Iacopetti , Elena Fattori , Gennaro Ciliberto
Konu :
Immunology, Immunology and Allergy
Yıl :
1992
Maria Teresa Fiorillo
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Kaydet Alıntıla
DOI : 10.1002/eji.1830221021
ISSN: 0014-2980
Sayı: 10
Cilt: 22
Sayfa: 2609-2615
9
The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
Frontiers in Immunology
Yazar(lar) :
Fabiana Paladini , Maria Teresa Fiorillo , Valentina Tedeschi , Benedetta Mattorre , Rosa Sorrentino
Yıl :
2020
Maria Teresa Fiorillo
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Kaydet Alıntıla
In the human genome, the aminopeptidases ERAP1, ERAP2 and LNPEP lie contiguously on chromosome 5. They share sequence homology, functions and associations with immune-mediated diseases. By analyzing their multifaceted activities as well as their expression in the zoological scale, we suggest here that the progenitor of the three aminopeptidases might be LNPEP from which the other two aminopeptidases could have derived by gene duplications. We also propose that their functions are partially redundant. More precisely, the evolutionary story of the three aminopeptidases might have been dictated by their role in regulating the renin–angiotensin system, which requires their controlled and coordinated expression. This hypothesis is supported by the many species that lack one or the other gene as well as by the lack of ERAP2 in rodents and a null expression in 25% of humans. Finally, we speculate that their role in antigen presentation has been acquired later on during evolution. They have therefore been diversified between those residing in the ER, ERAP1 and ERAP2, whose role is to refine the MHC-I peptidomes, and LNPEP, mostly present in the endosomal vesicles where it can contribute to antigen cross-presentation or move to the cell membrane as receptor for angiotensin IV. Their association with autoinflammatory/autoimmune diseases can therefore be two-fold: as “contributors” to the shaping of the immune-peptidomes as well as to the regulation of the vascular response.
DOI : 10.3389/fimmu.2020.01576
Anahtar Kelimeler : ERAP1, ERAP2, LNPEP, aminopeptidases, immune-mediated diseases
ISSN: 1664-3224
Cilt: 11
Sınıflandırma :
10
The interplay between the geographic distribution of HLA-B27 alleles and their role in infectious and autoimmune diseases: A unifying hypothesis
Dergi Makalesi

Dergi Makalesi
Kaynak :
Science Direct
Dergi:
Autoimmunity Reviews
Yayıncı:
Elsevier
Yazar(lar) :
Alessandro Mathieu , Fabiana Paladini , Alessandra Vacca , Alberto Cauli , Maria Teresa Fiorillo , Rosa Sorrentino
Yıl :
2009
Maria Teresa Fiorillo
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Kaydet Alıntıla
Due to its strong association with Ankylosing Spondylitis and the other Spondyloarthropathies, the HLA-B27 family of alleles and, in particular, the ancestral HLA-B⁎2705, has been the object of numerous studies. More recently, some novel interesting features have emerged such as the ability of HLA-B27 to confer resistance to the progression of HIV infection and to promote a spontaneous CD8+ T cell-mediated viral clearance of HCV. The co-occurrence of these protective and pathogenic features suggests a common ground, i.e. to promote a more pronounced immune/inflammatory response leading to an effective clearance of some pathogens on one side and to autoimmunity on the other. This might be due to the antigen presenting properties and/or to the co-inheritance of gene variants that contribute to an altered homeostasis in case of microbial infections or tissue injury. The existence of conserved HLA haplotypes have since long been thought to result from a selective pressure by some pathogens that have edited the immune response genes. The peculiar distribution of the ancestor HLA-B⁎2705 along a latitude-dependent gradient and the opposite distribution of their variants have suggested a correlation with endemic malaria. In this respect, Sardinia, a small Mediterranean island plagued by malaria, represents an interesting laboratory since its population is enriched in conserved HLA haplotypes and several genetic studies have disclosed their correlation with infectious and autoimmune diseases.
DOI : 10.1016/j.autrev.2009.01.003
ISSN: 1568-9972
Sayı: 5
Cilt: 8
Sayfa: 420-425
Sınıflandırma :
11
Editorial: Ankylosing Spondylitis and Related Immune-Mediated Disorders
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
Frontiers in Immunology
Yazar(lar) :
Maria Teresa Fiorillo , Nigil Haroon , Francesco Ciccia , Maxime Breban , Maxime Breban , Maxime Breban
Yıl :
2019
Maria Teresa Fiorillo
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Kaydet Alıntıla
DOI : 10.3389/fimmu.2019.01232
Anahtar Kelimeler : ankylosing spondylitis, HLA-B27 alleles, functional genomics, enthesitis, anti-TNF therapy
ISSN: 1664-3224
Cilt: 10
Sınıflandırma :
12
Ankylosing Spondylitis: A Trade Off of HLA-B27, ERAP, and Pathogen Interconnections? Focus on Sardinia
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
Frontiers in Immunology
Yazar(lar) :
Fabiana Paladini , Maria Teresa Fiorillo , Valentina Tedeschi , Alberto Cauli , Alessandro Mathieu , Rosa Sorrentino
Yıl :
2019
Maria Teresa Fiorillo
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 Piri Tam Metin Bulucu
Kaydet Alıntıla
The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for genetic association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to be associated with AS. The highly homogenous genetic structure of the Sardinian population has favored the search of relevant variants for disease-association studies. Moreover, malaria, once endemic in the island, has been shown to have contributed to shape the native population genome affecting the relative allele frequency of relevant genes. In Sardinia, the prevalence of HLA-B*2709, which differs from the strongly AS-associated B*2705 prototype for one amino acid (His/Asp116) in the F pocket of the peptide binding groove, is around 20% of all HLA-B27 alleles. We have previously hypothesized that malaria could have contributed to the establishment of this allele in Sardinia. Based on our recent findings, in this perspective article we speculate that the Endoplasmic Reticulum Amino Peptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria. These genes, besides shaping the immunopeptidome of HLA-class I molecules, have other biological functions that could also be involved in the immunosurveillance against malaria.
DOI : 10.3389/fimmu.2019.00035
Anahtar Kelimeler : HLA-B27 alleles, ankylosing spondylitis, ERAP1 and 2, autoimmunity, malaria
ISSN: 1664-3224
Cilt: 10
Sınıflandırma :
13
The expression of vasoactive intestinal peptide receptor 1 is negatively modulated by microRNA 525-5p.
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
PLoS ONE
Yazar(lar) :
Elisa Cocco , Fabiana Paladini , Giuseppe Macino , Valerio Fulci , Maria Teresa Fiorillo , Rosa Sorrentino
Yıl :
2010
Maria Teresa Fiorillo
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Kaydet Alıntıla
BACKGROUND: The human Vasoactive Intestinal Peptide (VIP) is a neurokine with effects on the immune system where it is involved in promoting tolerance. In this context, one of its receptors, VPAC1, has been found to be down-modulated in cells of the immune network in response to activating stimuli. In particular, the bacterial liposaccharide (LPS), a strong activator of the innate immune system, induces a rapid decrease of VPAC1 expression in monocytes and this event correlates with polymorphisms in the 3'-UTR of the gene. METHODOLOGY/PRINCIPAL FINDINGS: MicroRNA 525-5p, having as putative target the 3'-UTR region of VPAC1, has been analysed for its expression in monocytes and for its role in down-modulating VPAC1 expression. We report here that miR-525-5p is promptly up-regulated in LPS-treated monocytes. This microRNA, when co-transfected in 293T cells together with a construct containing the 3'-UTR of the VPAC1 gene, significantly reduced the luciferase activity in a standard expression assay. The U937 cell line as well as primary monocytes enforced to express miR-525-5p, both down-modulate VPAC1 expression at similar extent. CONCLUSIONS/SIGNIFICANCE: Our results show that the response to an inflammatory stimulus elicits in monocytes a rapid increase of miR-525-5p that targets a signaling pathway involved in the control of the immune homeostasis.
DOI : 10.1371/journal.pone.0012067
ISSN: 1932-6203
Cilt: 5
Sayı: 8
Sayfa: e12067
Sınıflandırma :
Biyotıp %100
Viroloji %19
14
Interaction Pattern of Arg 62 in the A-Pocket of Differentially Disease-Associated HLA-B27 Subtypes Suggests Distinct TCR Binding Modes
Araştırma Makalesi

Araştırma Makalesi
Open Access
Kaynak :
PLOS - Public Library of Science
Dergi:
Public Library of Science
Yazar(lar) :
Maria Teresa Fiorillo , Rainer A. Böckmann , Rosa Sorrentino , Silvana Caristi , Valentina Tedeschi , Alessandro Mathieu , Alberto Cauli , Daniele Narzi , Elisa Nurzia
Yıl :
2012
Maria Teresa Fiorillo
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Kaydet Alıntıla
The single amino acid replacement Asp116His distinguishes the two subtypes HLA-B*2705 and HLA-B*2709 which are, respectively, associated and non-associated with Ankylosing Spondylitis, an autoimmune chronic inflammatory disease. The reason for this differential association is so far poorly understood and might be related to subtype-specific HLA:peptide conformations as well as to subtype/peptide-dependent dynamical properties on the nanoscale. Here, we combine functional experiments with extensive molecular dynamics simulations to investigate the molecular dynamics and function of the conserved Arg62 of the α1-helix for both B27 subtypes in complex with the self-peptides pVIPR (RRKWRRWHL) and TIS (RRLPIFSRL), and the viral peptides pLMP2 (RRRWRRLTV) and NPflu (SRYWAIRTR). Simulations of HLA:peptide systems suggest that peptide-stabilizing interactions of the Arg62 residue observed in crystal structures are metastable for both B27 subtypes under physiological conditions, rendering this arginine solvent-exposed and, probably, a key residue for TCR interaction more than peptide-binding. This view is supported by functional experiments with conservative (R62K) and non-conservative (R62A) B*2705 and B*2709 mutants that showed an overall reduction in their capability to present peptides to CD8+ T cells. Moreover, major subtype-dependent differences in the peptide recognition suggest distinct TCR binding modes for the B*2705 versus the B*2709 subtype.
DOI : 10.1371/journal.pone.0032865
Anahtar Kelimeler : Crystal structure, T cell receptors, T cells, HeLa cells, Salt bridges, Biochemical simulations, Major histocompatibility complex, Molecular dynamics
Sınıflandırma :
15
A sardinian patient with ankylosing spondylitis and HLA–B*2709 co-occurring with HLA–B*1403
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
Arthritis & Rheumatism
Yazar(lar) :
Alberto Cauli , Alessandra Vacca , Antonella Mameli , Giuseppe Passiu , Maria Teresa Fiorillo , Rosa Sorrentino , Alessandro Mathieu
Konu :
Immunology, Immunology and Allergy, Pharmacology (medical), Rheumatology
Yıl :
2007
Maria Teresa Fiorillo
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Tam Metin
Kaydet Alıntıla
DOI : 10.1002/art.22819
ISSN: 0004-3591
Sayı: 8
Cilt: 56
Sayfa: 2807-2809
16
CD8+ T-cell mediated self-reactivity in HLA-B27 context as a consequence of dual peptide conformation
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Dergi Makalesi
Kaynak :
Science Direct
Dergi:
Clinical Immunology
Yayıncı:
Elsevier
Yazar(lar) :
Elisa Nurzia , Francesca Panimolle , Alberto Cauli , Alessandro Mathieu , Adriana Magnacca , Fabiana Paladini , Rosa Sorrentino , Maria Teresa Fiorillo
Yıl :
2010
Maria Teresa Fiorillo
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
HLA-B⁎2709 does not predispose for Ankylosing Spondylitis although it differs from B⁎2705, the most common and AS-associated subtype in different ethnic groups, only for the substitution His116Asp. Therefore, a productive approach to elucidate the molecular mechanisms of the disease could be the comparison of these alleles. B⁎2705 has been shown to display certain self-peptides enriched in basic residues i.e., pVIPR and pGR, in a dual conformation and this is accompanied by the presence of specific cytotoxic T cells in patients with AS. In this study, we convalidate our previous observation that B⁎2709 healthy subjects do not possess primary reactivity towards pVIPR while showing a prompt CD8+ T cell response driven by pGR. Notably, in the B⁎2709 context of presentation, pVIPR assumes only a single conformation in contrast with pGR which is dimorphic. These results suggest a possible general connection between the occurrence of double peptide conformation and the property of inducing specific autoimmune responses.
DOI : 10.1016/j.clim.2010.01.009
Anahtar Kelimeler : Ankylosing Spondylitis, HLA-B27 alleles, CD8+ T lymphocytes, Autoimmunity, Self-peptides, Autoreactivity, Dual peptide-binding mode
ISSN: 1521-6616
Sayı: 3
Cilt: 135
Sayfa: 476-482
Sınıflandırma :
17
Single nucleotide polymorphisms in the 3'UTR of VPAC-1 cooperate in modulating gene expression and impact differently on the interaction with miR525-5p.
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
PLoS ONE
Yazar(lar) :
Fabiana Paladini , Nicla Porciello , Giorgio Camilli , Sinem Tuncer , Elisa Cocco , Maria Teresa Fiorillo , Rosa Sorrentino
Yıl :
2014
Maria Teresa Fiorillo
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
Complex immune and neurodegenerative disorders are the result of multiple interactions between common genetic variations having, individually, a weak effect on the disease susceptibility or resistance. Interestingly, some genes have been found to be associated with more than one disease although not necessarily the same SNPs are involved. In this context, single nucleotide polymorphisms in the 3'UTR region of type 1 receptor (VPAC-1) for vasoactive intestinal peptide (VIP) have been reported to be associated with some immune-mediated as well as with neurodegenerative diseases such as Alzheimer's Disease (AD). Here, we demonstrate that variations at the 3'UTR of the VPAC-1 gene act synergistically to affect the expression of the luciferase as well as of the GFP reporter genes expressed in HEK293T cells. Moreover, the miRNA 525-5p, previously shown by us to target the 3'UTR of VPAC-1, is more efficient in decreasing GFP expression when co-expressed with constructs carrying the allele C at rs896 (p<10(-3)) suggesting that this miRNA regulates VPAC-1 expression at different levels depending on rs896 polymorphism and thus adding complexity to the network of disease susceptibility.
DOI : 10.1371/journal.pone.0112646
ISSN: 1932-6203
Cilt: 9
Sayı: 11
Sayfa: e112646
18
The naturally occurring polymorphism Asp116 → His116 , differentiating the ankylosing spondylitis-associated HLA-B*2705 from the non-associated HLA-B*2709 subtype, influences peptide-specific CD8 T cell recognition
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
European Journal of Immunology
Yazar(lar) :
Maria Teresa Fiorillo , Giulia Greco , Monica Maragno , Ilaria Potolicchio , Andrea Monizio , Maria Luisa Dupuis , Rosa Sorrentino
Konu :
Immunology, Immunology and Allergy
Yıl :
1998
Maria Teresa Fiorillo
Yayıncı Web Sitesi
Tam Metin
Kaydet Alıntıla
HLA‐B27 molecules are interesting because of their strong association with ankylosing spondylitis (AS) and reactive arthritis (ReA). A pathogenetic role for these molecules has been postulated in presenting a putative ‐‐bb‐‐arthritogenic peptide to CD8 T cells. The HLA‐B*2709 subtype, although differing by a single amino acid (His116 → Asp116 ) from the wide spread and strongly AS‐associated subtype HLA‐B*2705, is not found in patients. Since residue 116 interacts with the C terminus of the peptide, it is possible that the two subtypes differ in their antigen‐presenting features. We show here that CD8 T cells can distinguish the two HLA‐B27 subtypes when presenting a same epitope derived from Epstein‐Barr virus‐latent membrane protein 2. Moreover, alanine scanning mutagenesis analysis revealed that the peptide residues relevant for such recognition are different depending on whether HLA‐B*2705 or ‐B*2709 molecules present the epitope. These results give support to the belief that functional differences determined by subtype‐specific polymorphisms can have a pathogenetic relevance and open up a new scenario where subtle modifications within the peptide/HLA ligand might be responsible for the differential association between HLA‐B27 subtypes and spondyloarthropathies.
DOI : 10.1002/(sici)1521-4141(199808)28:08<2508::aid-immu2508>3.0.co;2-1
ISSN: 0014-2980
Sayı: 8
Cilt: 28
Sayfa: 2508-2516
19
The Ankylosing Spondylitis-Associated HLA-B*2705 Presents a B*0702-Restricted EBV Epitope and Sustains the Clonal Amplification of Cytotoxic T Cells in Patients
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Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Dergi:
Molecular Medicine
Yazar(lar) :
Valentina Tedeschi , Carolina Vitulano , Alberto Cauli , Fabiana Paladini , Matteo Piga , Alessandro Mathieu , Rosa Sorrentino , Maria Teresa Fiorillo
Yıl :
2016
Maria Teresa Fiorillo
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Kaydet Alıntıla
Abstract HLA-B*27 is strongly associated with an inflammatory autoimmune disorder, the Ankylosing Spondylitis (AS) and plays a protective role in viral infections. The two aspects might be linked. In this work, we compared in B*2705/B*07 positive patients with AS, the CD8+ T cell responses to two immunodominant EBV-derived epitopes restricted for either the HLA-B*27 (pEBNA3C) or the HLA-B*07 (pEBNA3A). We have unexpectedly found that the HLA-B*07-restricted EBNA3A peptide is presented by both the B*0702 and the B*2705 but not by the non AS-associated B*2709, that differs from the AS-associated B*2705 for a single amino acid in the peptide-binding groove (His116Asp). We then analyzed 38 B*2705-positive/B*07-negative (31 AS-patients and 7 healthy donors) and 8 B*2709-positive/B*07-negative subjects. EBNA3A-specific CD8+ T lymphocytes were present in 55.3% of the HLA-B*2705 but in none of the B*2709 donors (p = 0.0049). TCR β-chain analysis identified common TCRBV and TCRBJ gene segments and shared CDR3β sequences in pEBNA3A-responsive CTLs of B*2705 carriers, suggesting the existence of a shared TCR repertoire for recognition of the uncanonical B*2705/pEBNA3A complex. These data highlight the plasticity of the AS-associated HLA-B*2705, which presents peptides with suboptimal binding motifs, possibly contributing both to its enhanced capacity to protect against pathogens and to predispose to autoimmunity.
DOI : 10.2119/molmed.2016.00031
Cilt: 22
Sayı: 1
Sayfa: 215 - 223
Sınıflandırma :
Viroloji %50
20
Susceptibility to ankylosing spondylitis correlates with the C-terminal residue of peptides presented by various HLA-B27 subtypes
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Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
European Journal of Immunology
Yazar(lar) :
Maria Teresa Fiorillo , Leslie Meadows , Mauro D'Amato , Jeffrey Shabanowitz , Donald F. Hunt , Ettore Appella , Rosa Sorrentino
Yıl :
1997
Maria Teresa Fiorillo
Yayıncı Web Sitesi
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Kaydet Alıntıla
Susceptibility to spondyloarthropaties is strongly associated with some HLA‐B27 alleles. Evidence suggests a direct pathogenic role for the B27 molecules which possibly present an arthritogenic peptide to the T cells. If this hypothesis is true, B27 subtypes that differ structurally but are disease‐associated ought to be capable of presenting such peptide(s), while non‐disease‐associated ones would not. We have recently described a B27 subtype, B*2709, and shown its absence in ankylosing spondylitis (AS) patients. Here, we show the elution and sequence of peptides from HLA‐B*2709 molecules. Similar to other B27 subtypes, these peptides are mainly nonamers with an Arg at position P2. Comparison of the C‐terminal anchors of peptides eluted from B*2702 and B*2705 with those eluted from B*2709 reveals that, while B*2702 and B*2705 have a broader specificity, B*2709 molecules appear to only accept C‐terminal hydrophobic residues. A common feature shared by the two caucasoid AS‐associated subtypes (B*2702 and B*2705) but different from B*2709, is the presence of a Tyr as peptide C‐terminal anchor. The substitution of Val for Tyr at the C terminus in one of the eluted peptides greatly reduces the binding to B*2709 molecules. This finding suggests Tyr as a discriminative amino acid allowed at the C terminus of peptides bound to the AS‐associated B27 subtypes, but not to those which are not associated with AS.
DOI : 10.1002/eji.1830270205
ISSN: 0014-2980
Sayı: 2
Cilt: 27
Sayfa: 368-373
21
Identification of previously unrecognized predisposing factors for ankylosing spondylitis from analysis of HLA–B27 extended haplotypes in sardinia
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
Arthritis & Rheumatism
Yazar(lar) :
Isabella Cascino , Fabiana Paladini , Francesca Belfiore , Alberto Cauli , Claudia Angelini , Maria Teresa Fiorillo , Alessandro Mathieu , Rosa Sorrentino
Konu :
Immunology, Immunology and Allergy, Pharmacology (medical), Rheumatology
Yıl :
2007
Maria Teresa Fiorillo
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Kaydet Alıntıla
DOI : 10.1002/art.22820
ISSN: 0004-3591
Sayı: 8
Cilt: 56
Sayfa: 2640-2651
22
Regulation and trafficking of the HLA-E molecules during monocyte-macrophage differentiation
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
Journal of Leukocyte Biology
Yazar(lar) :
Giorgio Camilli , Antonino Cassotta , Simone Battella , Gabriella Palmieri , Angela Santoni , Fabiana Paladini , Maria Teresa Fiorillo , Rosa Sorrentino
Konu :
Immunology, Cell Biology
Yıl :
2015
Maria Teresa Fiorillo
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Kaydet Alıntıla
HLA‐E is a nonclassical HLA‐class I molecule whose best known role is to protect from the natural killer cells. More recently, an additional function more similar to that of classical HLA‐class I molecules, i.e., antigen presentation to T cells, is emerging. However, much remains to be explored about the intracellular trafficking of the HLA‐E molecules. With the use of 3 different cellular contexts, 2 monocytic cell lines, U937 and THP1, and peripheral blood monocytes, we show here a remarkable increase of HLA‐E during monocyte‐macrophage differentiation. This goes independently from the classical HLA‐class I, the main source of HLA‐E‐specific peptides, which is found strongly up‐regulated upon differentiation of peripheral blood monocytes but not at all in the case of U937 and THP1 cell lines. Although in all cases, there was a moderate increase of HLA‐E expressed in the cell surface, lysis by natural killer cells is comparably restored by an anti‐NKG2A antibody in untreated as well as in PMA‐differentiated U937 cells. Instead, the great majority of the HLA‐E is retained in the vesicles of the autophagy‐lysosome network, where they colocalize with the microtubule‐associated protein light chain 3, as well as with the lysosomal‐associated membrane protein 1. We conclude that differently from the classical HLA‐class I molecules, the primary destination of the newly synthesized HLA‐E molecules in macrophages is, rather than the cell membrane, the intracellular autophagy‐lysosomal vesicles where they are stored and where they can encounter the exogenous antigens.
DOI : 10.1189/jlb.1a0415-172r
ISSN: 0741-5400
Sayı: 1
Cilt: 99
Sayfa: 121-130
23
Relevance of residue 116 of HLA-B27 in determining susceptibility to ankylosing spondylitis
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
European Journal of Immunology
Yazar(lar) :
Mauro D'amato , Maria Teresa Fiorillo , Carlo Carcassi , Alessandro Mathieu , Angelo Zuccarelli , Pier Paolo Bitti , Roberto Tosi , Rosa Sorrentino
Konu :
Immunology, Immunology and Allergy
Yıl :
1995
Maria Teresa Fiorillo
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Kaydet Alıntıla
DOI : 10.1002/eji.1830251133
ISSN: 0014-2980
Sayı: 11
Cilt: 25
Sayfa: 3199-3201
24
Characterization of CD8+ T cell repertoire in identical twins discordant and concordant for multiple sclerosis
Dergi Makalesi

Dergi Makalesi
Kaynak :
Wiley Online Library
Dergi:
Journal of Leukocyte Biology
Yazar(lar) :
Paolo Somma , Giovanni Ristori , Luca Battistini , Stefania Cannoni , Giovanna Borsellino , Adamo Diamantini , Marco Salvetti , Rosa Sorrentino , Maria Teresa Fiorillo
Yıl :
2006
Maria Teresa Fiorillo
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Kaydet Alıntıla
Autoreactive CD4+ and CD8+ T cells directed against CNS autoantigens may play a role in the development of multiple sclerosis (MS). Identical twins share the same genetic background but not the TCR repertoire that is shaped by the encounter with self or foreign antigens. To gain insights into the interplay between MS and T cell repertoire, peripheral blood CD4+ and CD8+ T lymphocytes and their CCR7+/CCR7– subsets from five pairs of identical twins (four discordant and one concordant for MS; none of which had taken disease‐modifying therapy) were compared by TCR β‐chain (TCRB) complementary‐determining region 3 (CDR3) spectratyping. CD4+ T cells generally showed a Gaussian distribution, whereas CD8+ T cells exhibited subject‐specific, widely skewed TCR spectratypes. There was no correlation between CD8+ T cell oligoclonality and disease. Sequencing of predominant spectratype expansions revealed shared TCRB‐CDR3 motifs when comparing inter‐ and/or intrapair twin members. In many cases, these sequences were homologous to published TCRs, specific for viruses implicated in MS pathogenesis, CNS autoantigens, or copaxone [glatiramer acetate (GA)], implying the occurrence of naturally GA‐responding CD8+ T cells. It is notable that these expanded T cell clones with putative pathogenic or regulatory properties were present in the affected as well as in the healthy subject, thus suggesting the existence of a “MS predisposing trait” shared by co‐twins discordant for MS.
DOI : 10.1189/jlb.0906584
ISSN: 0741-5400
Sayı: 3
Cilt: 81
Sayfa: 696-710
25
AIF-1 gene does not confer susceptibility to Behçet's disease: Analysis of extended haplotypes in Sardinian population.
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
PubMed
Dergi:
PLoS ONE
Yazar(lar) :
Maria Maddalena Angioni , Matteo Piga , Fabiana Paladini , Sara Lai , Gian Luca Erre , Alberto Floris , Alberto Cauli , Maria Teresa Fiorillo , Giuseppe Passiu , Carlo Carcassi , Rosa Sorrentino , Alessandro Mathieu
Yıl :
2018
Maria Teresa Fiorillo
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 Piri Tam Metin Bulucu
Kaydet Alıntıla
Behçet's disease (BD) is a polygenic immune-mediated disorder characterized by a close association with the HLA-B*51 allele. The HLA region has a strong linkage disequilibrium (LD) and carries several genetic variants (e.g. MIC-A, TNF-α genes) identified as associated to BD because of their LD with HLA-B*51. In fact, the HLA-B*51 is inherited as part of extended HLA haplotypes which are well preserved in patients with BD. Sardinian population is highly differentiated from other Mediterranean populations because of a distinctive genetic structure with very highly preserved HLA haplotypes.
DOI : 10.1371/journal.pone.0204250
Sınıflandırma :
26
Unusual Placement of an EBV Epitope into the Groove of the Ankylosing Spondylitis-Associated HLA-B27 Allele Allows CD8+ T Cell Activation
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
Directory of Open Access Journals (DOAJ)
Yazar(lar) :
Valentina Tedeschi , Josephine Alba , Fabiana Paladini , Marino Paroli , Alberto Cauli , Alessandro Mathieu , Rosa Sorrentino , Marco Du2019Abramo , Maria Teresa Fiorillo
Yıl :
2019
Maria Teresa Fiorillo
Piri Tam Metin Bulucu
Kaydet Alıntıla
The human leukocyte antigen HLA-B27 is a strong risk factor for Ankylosing Spondylitis (AS), an immune-mediated disorder affecting axial skeleton and sacroiliac joints. Additionally, evidence exists sustaining a strong protective role for HLA-B27 in viral infections. These two aspects could stem from common molecular mechanisms. Recently, we have found that the HLA-B*2705 presents an EBV epitope (pEBNA3A-RPPIFIRRL), lacking the canonical B27 binding motif but known as immunodominant in the HLA-B7 context of presentation. Notably, 69% of B*2705 carriers, mostly patients with AS, possess B*2705-restricted, pEBNA3A-specific CD8+ T cells. Contrarily, the non-AS-associated B*2709 allele, distinguished from the B*2705 by the single His116Asp polymorphism, is unable to display this peptide and, accordingly, B*2709 healthy subjects do not unleash specific T cell responses. Herein, we investigated whether the reactivity towards pEBNA3A could be a side effect of the recognition of the natural longer peptide (pKEBNA3A) having the classical B27 consensus (KRPPIFIRRL). The stimulation of PBMC from B*2705 positive patients with AS in parallel with both pEBNA3A and pKEBNA3A did not allow to reach an unambiguous conclusion since the differences in the magnitude of the response measured as percentage of IFNγ-producing CD8+ T cells were not statistically significant. Interestingly, computational analysis suggested a structural shift of pEBNA3A as well as of pKEBNA3A into the B27 grooves, leaving the A pocket partially unfilled. To our knowledge this is the first report of a viral peptide: HLA-B27 complex recognized by TCRs in spite of a partially empty groove. This implies a rethinking of the actual B27 immunopeptidome crucial for viral immune-surveillance and autoimmunity.
DOI : 10.3390/cells8060572
Anahtar Kelimeler : HLA-B27, viral peptides, computational analysis, ankylosing spondylitis
ISSN: 2073-4409
Cilt: 8
Sayı: 6
Sayfa: 572
Sınıflandırma :
27
Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis.
Dergi Makalesi

Dergi Makalesi
Open Access
Kaynak :
PubMed
Dergi:
RMD Open
Yazar(lar) :
Alberto Cauli , Grazia Dessole , Matteo Piga , Maria Maddalena Angioni , Silvia Pinna , Alberto Floris , Mattia Congia , Enrico Mascia , Fabiana Paladini , Valentina Tedeschi , Rosa Sorrentino , Maria Teresa Fiorillo , Alessandro Mathieu
Yıl :
2018
Maria Teresa Fiorillo
Yayıncı Web Sitesi
 Piri Tam Metin Bulucu
Kaydet Alıntıla
Ankylosing spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of human leucocyte antigen (HLA)-B27 alleles. HLA-E molecules are non-classical major histocompatibility complex (MHC) class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis.''.
DOI : 10.1136/rmdopen-2017-000597
Anahtar Kelimeler : ankylosing spondylitis, inflammation, spondyloarthritis
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