Cytotoxic T cell activity against peptides of Hu protein in anti-Hu syndrome |
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Authors: | Tanaka Masami Maruyama Yoshie Sugie Miho Motizuki Hitoshi Kamakura Keiko Tanaka Keiko |
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Affiliation: | Department of Neurology and Clinical Research Center, National Nishi-Niigata Central Hospital, 1-14-1 Masago, 950-2085, Niigata, Japan. masami@masa.go.jp |
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Abstract: | Half of all patients with limbic encephalitis and small cell lung carcinoma (SCLC) have anti-Hu antibodies that react with all of central and peripheral nervous system neuronal nuclei in immunohistochemical studies and 35- to 40-kDa reactive bands on western blots of extracts from isolated central nervous system neurons. The roles of anti-Hu antibodies in neuronal damage, however, have yet to be shown. Evidence of infiltration of CD8-positive T cells to tumors and affected nervous tissues and limited use of the T cell receptor repertoire in the central nervous system suggests that CD8-positive cytotoxic T cells (CTL) cause neuronal loss. We found the HLA B7 supertype in all of seven Japanese patients with anti-Hu syndrome. We identified HLA class I-restricted, CD 8-positive cytotoxic T cell activity in peripheral blood from three patients with anti-Hu syndrome for five peptides with binding motifs for the HLA B7 supertype in the amino acid sequence of the Hu protein. This study support the involvement of CD8-positive cytotoxic T cells in the development of paraneoplastic neurological syndrome with anti-Hu antibodies. |
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