Cellular immune response to human renal-cell carcinomas: definition of a common antigen recognized by HLA-A2-restricted cytotoxic T-lymphocyte (CTL) clones.
Cytotoxic T lymphocyte (CTL) clones directed against autologous renal-cell carcinoma (RCC) cell lines were generated by mixed lymphocyte/tumor-cell culture (MLTC) using peripheral blood lymphocytes (PBL). A CD8+, CD4- CTL clone MZ1257-CTL 5/30 with high cytolytic activity for the autologous tumor cell line MZ1257-RCC was established. No lysis of the autologous EBV-transformed B lymphocytes (EBV-B) or K562 cells was observed. A panel of HLA-A2-matched allogeneic RCC lines was recognized by CTL 5/30. Further specificity analysis showed a cross-reactivity with HLA-A2-matched allogeneic tumor cells of various origins, especially melanoma. CTL 5/30 was also cross-reactive with several HLA-A2-positive allogeneic normal kidney cells in culture. The restriction element identified for CTL 5/30 was HLA-A2, as shown by blocking of cytotoxicity using an anti-HLA-A2 monoclonal antibody (MAb) and by resistance of an HLA-A2-negative melanoma variant SK29-MEL. 1.22 against lysis by CTL 5/30. In this report we demonstrate HLA-A2-restricted recognition of a T-cell-defined antigen on autologous renal-cancer cells. This antigen is also expressed and recognized in association with HLA-A2 on normal kidney cells in culture and other HLA-A2-positive tumor cells. It may therefore be a normal differentiation antigen to which tolerance is incomplete in the renal-cell cancer system investigated.
Bernhard
H
H
Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität, Mainz, Germany.
Karbach
J
J
Wölfel
T
T
Busch
P
P
Störkel
S
S
Stöckle
M
M
Wölfel
C
C
Seliger
B
B
Huber
C
C
Meyer zum Büschenfelde
K H
KH
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007668:Kidney / Q000276:immunology; D007680:Kidney Neoplasms / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I