瑞士苏黎世大学Roland Martin研究小组发现，HLA-DR15分子联合塑造多发性硬化症中的自身反应性T细胞库。该研究于2020年10月21日在线发表于国际一流学术期刊《细胞》。

Title: HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis

Author: Jian Wang, Ivan Jelcic, Lena Mühlenbruch, Veronika Haunerdinger, Nora C. Toussaint, Yingdong Zhao, Carolina Cruciani, Wolfgang Faigle, Reza Naghavian, Magdalena Foege, Thomas M.C. Binder, Thomas Eiermann, Lennart Opitz, Laura Fuentes-Font, Richard Reynolds, William W. Kwok, Julie T. Nguyen, Jar-How Lee, Andreas Lutterotti, Christian Münz, Hans-Georg Rammensee, Mathias Hauri-Hohl, Mireia Sospedra, Stefan Stevanovic, Roland Martin

Issue&Volume: 2020-10-21

Abstract: The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4+ T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells. Furthermore, we identified autoreactive CD4+ T cell clones that can cross-react with HLA-DR-derived self-peptides (HLA-DR-SPs), peptides from MS-associated foreign agents (Epstein-Barr virus and Akkermansia muciniphila), and autoantigens presented by DR2a and DR2b. Thus, both HLA-DR15 allomorphs jointly shape an autoreactive T cell repertoire by serving as antigen-presenting structures and epitope sources and by presenting the same foreign peptides and autoantigens to autoreactive CD4+ T cells in MS.

DOI: 10.1016/j.cell.2020.09.054

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31251-4