title: 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.
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 analysed 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.
authors.affiliation: Department of Biology and Biotechnology "C. Darwin", Sapienza University, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tedeschi
authors.affiliation: Department of Biology and Biotechnology "C. Darwin", Sapienza University, Rome, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Vitulano
authors.affiliation: 2nd Chair of Rheumatology, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cauli
authors.affiliation: Department of Biology and Biotechnology "C. Darwin", Sapienza University, Rome, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Paladini
authors.affiliation: 2nd Chair of Rheumatology, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Piga
authors.affiliation: 2nd Chair of Rheumatology, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mathieu
authors.affiliation: Department of Biology and Biotechnology "C. Darwin", Sapienza University, Rome, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sorrentino
authors.affiliation: Department of Biology and Biotechnology "C. Darwin", Sapienza University, Rome, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Fiorillo
keywords: Ankylosing Spondylitis; CD8+ T lymphocytes; Epstein Barr virus; HLA-B*27; atypical peptide presentation