CD4(+), HLA class I-restricted, cytolytic T-lymphocyte clone against primary malignant melanoma cells.
The involvement of HLA-class I in target cell lysis by CD4(+) cytolytic T cells (CTL) has been a controversial issue. A CTL clone of CD4 phenotype was derived from the peripheral blood lymphocytes of a patient with primary melanoma. The CTL clone stably lysed the autologous primary melanoma cells for approximately 9 months in culture. Both the Valpha2/Vbeta8 T-cell receptor and CD4 were involved in CTL cytotoxicity. Of a large panel of allogeneic primary and metastatic melanoma or colorectal carcinoma cells, autologous and allogeneic Epstein-Barr virus-transformed B cells and autologous fibroblasts, only allogeneic metastatic melanoma cells matched with the autologous tumor cells for HLA-class I (B57[17]) were lysed and induced IFN-gamma secretion by the CTL clone. Lysis of the autologous tumor cells was significantly blocked by monoclonal antibody to HLA-B17. Importantly, allogeneic, HLA-class I- and class II-unmatched melanoma cells were lysed by the CTL only following transfection of the cells with B57[17] cDNA. Our results provide direct evidence for the involvement of both CD4 and HLA-class I in tumor cell lysis by CD4(+) CTL.
Somasundaram
R
R
The Wistar Institute, Philadelphia, PA 19104, USA.
Robbins
P
P
Moonka
D
D
Loh
E
E
Marincola
F
F
Patel
A
A
Guerry
D
D
Herlyn
D
D
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016207:Cytokines; D018076:DNA, Complementary; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell