title: HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis.
abstract: It was hypothesized that the EBV-specific CD8(+) T cell response may be dysregulated in multiple sclerosis (MS) patients, possibly leading to a suboptimal control of this virus. To examine the CD8(+) T cell response in greater detail, we analyzed the HLA-A2-, HLA-B7-, and HLA-B8-restricted EBV- and CMV-specific CD8(+) T cell responses in a high number of MS patients and control subjects using tetramers. Content in cytolytic granules, as well as cytotoxic activity, of EBV- and CMV-specific CD8(+) T cells was assessed. We found that MS patients had a lower or a higher prevalence of HLA-A2 and HLA-B7, respectively. Using HLA class I tetramers in HLA-B7(+) MS patients, there was a higher prevalence of MS patients with HLA-B*0702/EBV(RPP)-specific CD8(+) T cells ex vivo. However, the magnitude of the HLA-B*0702/EBV(RPP)-specific and HLA-B*0702/CMV(TPR)-specific CD8(+) T cell response (i.e., the percentage of tetramer(+) CD8(+) T cells in a study subject harboring CD8(+) T cells specific for the given epitope) was lower in MS patients. No differences were found using other tetramers. After stimulation with the HLA-B*0702/EBV(RPP) peptide, the production of IL-2, perforin, and granzyme B and the cytotoxicity of HLA-B*0702/EBV(RPP)-specific CD8(+) T cells were decreased. Altogether, our findings suggest that the HLA-B*0702-restricted viral (in particular the EBV one)-specific CD8(+) T cell response is dysregulated in MS patients. This observation is particularly interesting knowing that the HLA-B7 allele is more frequently expressed in MS patients and considering that EBV is associated with MS.
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, University Hospital of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Samantha
authors.initials: S
authors.lastname: Jilek
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.forename: Mathieu
authors.initials: M
authors.lastname: Canales
authors.forename: Andreas
authors.initials: A
authors.lastname: Lysandropoulos
authors.forename: Anastasia
authors.initials: A
authors.lastname: Zekeridou
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Renaud A
authors.initials: RA
authors.lastname: Du Pasquier
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D015793:HLA-B7 Antigen / Q000276:immunology*; D015795:HLA-B8 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications / Q000276:immunology* / Q000473:pathology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D015795:HLA-B8 Antigen