HLA-B7-restricted EBV-specific CD8+ T cells are dysregulated in multiple sclerosis

J Immunol. 2012 May 1;188(9):4671-80. doi: 10.4049/jimmunol.1103100. Epub 2012 Mar 28.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Epitopes, T-Lymphocyte / immunology*
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / pathology
  • Female
  • HLA-A2 Antigen / immunology
  • HLA-B7 Antigen / immunology*
  • HLA-B8 Antigen / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Male
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / pathology


  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • HLA-B*07:02 antigen
  • HLA-B7 Antigen
  • HLA-B8 Antigen