4.5 Article

Cytotoxic T cell activity against peptides of Hu protein in anti-Hu syndrome

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JOURNAL OF THE NEUROLOGICAL SCIENCES
卷 201, 期 1-2, 页码 9-12

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ELSEVIER SCIENCE BV
DOI: 10.1016/S0022-510X(02)00157-0

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paraneoplastic limbic encephalitis; anti-Hu antibody; small cell lung carcinoma; cytotoxic T cells; reverse immunogenetics; HLA supertype

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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 137 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 137 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. (C) 2002 Elsevier Science B.V. All rights reserved.

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