MHC-restricted responses of CD8+ and CD4+ T-cell clones from regional lymph nodes of melanoma patients.
Regional lymph-node (LN) lymphocytes may constitute an important defence against the spread of human melanoma beyond regional LNs. The present study was directed to clonal analysis of lymphocytes cultured either directly from the LNs or after stimulation in cultures with autologous melanoma (MLTC). T-cell clones derived from MLTC reactions had either CD4+ or CD8+ phenotypes. Inhibition studies with monoclonal antibodies (MAbs) suggested that the CD8+ cytotoxic T-cell (CTL) clones had MHC-class-I-restricted cytotoxic activity against the autologous and a proportion of HLA-class-I-compatible allogeneic melanomas. The pattern of cytotoxicity against a panel of HLA-typed melanoma cells and inhibition by (polyclonal) HLA-typing sera suggested the CD8+ CTL were restricted by HLA-A3. The CD4+ T-cell clones had weak cytotoxic activity which appeared restricted by HLA-DR2. T cells cultured from unstimulated lymphocytes were all CD4+. One of the clones exhibited cytotoxic activity against both the autologous and HLA-DR2-compatible allogeneic melanoma cells, whereas another 2 had cytotoxic activity only against a HLA-DR2-compatible allogeneic melanoma established from a primary melanoma. IL-2 production by a 4th non-cytotoxic clone had similar specificity. These results suggest that HLA-A3 and DR2 may act as restricting elements in recognition of melanoma antigens by T cells from LNs and that they may have recognized at least 2 different antigens on the melanoma cells.
Chen
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Immunology and Oncology Unit, Newcastle Mater Misericordiae Hospital, N.S.W., Australia.
Hersey
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P
D000368:Aged; D002455:Cell Division; D015788:HLA-A1 Antigen / Q000276:immunology; D015791:HLA-A3 Antigen / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D015788:HLA-A1 Antigen; D015791:HLA-A3 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2