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Reduced expression of peptide‐loaded HLA class I molecules on multiple sclerosis lymphocytes
Author(s) -
Li Fangqin,
Linan Mercedes J.,
Stein Marchion C.,
Faustman Denise L.
Publication year - 1995
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410380205
Subject(s) - human leukocyte antigen , multiple sclerosis , immunology , peripheral blood mononuclear cell , antigen , antigen presentation , medicine , biology , t cell , immune system , in vitro , genetics
Lymphocytes from patients with HLA class II–linked autoimmune disease such as type I diabetes, systemic lupus erythematosus, rheumatoid arthritis, and Graves' have recently been shown to have a Decemberrease in the expression of self‐peptide–filled HLA calss I antigens on the surface of peripheral lymphocytes. The human demyelinating diseases of multiple sclerosis in some cases are also associated with the presence of certain HLA class II genes, which may in turn be linked to genes in the class II region that control class I expression. Hence, we studied fresh peripheral blood mononuclear cells (PBMCs) and newly produced Epstein‐Barr virus (EBV)‐transformed cell lines from multiple sclerosis patients for the class I defect. Unseparated PBMCs, as well as T cells, B cells, and macrophages from multiple sclerosis patients had a Decemberrease in the amount of conformationally correct peptide‐filled HLA class I molecules on the cell surface compared with matched controls detectable by flow cytometry. To demonstrate the independence of this defect from exogenous serum factors, newly produced EBV‐transformed cell lines from B cells of patients with multiple sclerosis maintained the defect. In addition, DR2 +/+, +/–, and –/– EBV –transformed B cells from these patients similarly demonstrated the self‐antigen presentation defect. Analysis of a set of discordant multiple sclerosis twins revealed the class I defect was exclusively found on the affected twin lymphocytes, suggesting a role of this class I complex in disease expression. These data indicate that multiple sclerosis patients have abnormal presentation of self‐antigens. This phenomenon, common to a number of HLA‐linked autoimmune disorders, may be associated with failed self‐tolerance and improper T‐cell education secondary to faulty HLA class I assembly controlled by HLA class II linked genes.