Role of MHC class-I antigens and the CD3 complex in the lysis of autologous human tumours by T-cell clones.
Peripheral blood lymphocytes (PBL) of 4 patients with malignant effusions were stimulated for 6 days with purified autologous tumour cells, before isolation of the lymphoblasts and cloning by limiting dilution in interleukin-2 (IL-2). Forty-five clones were analyzed for cytotoxicity (CTX) against autologous, allogeneic tumour and erythromyeloid K562 cells of known status with respect to expression of major histocompatibility complex (MHC) antigens, estimated by reaction with the W6/32 (anti HLA, -A, -B, -C monomorphic) and TDR 31.1 (anti HLA-DR) monoclonal antibodies (MAb). All 45 clones were CD3+. Twenty-five (56%) of them were cytotoxic for at least one target; 24 were autoreactive (restricted in 7); 17 were alloreactive; 16 were K562 reactive. Under comparable conditions autoreactivity was partially blocked by W6/32 in 12/20 effector:target combinations; alloreactivity in 8/13 and K562 reactivity in 0/14. Modulation of effector cell surface CD3 antigens by OKT3 monitored by flow cytometry reduced autoreactivity in 9/14 combinations, alloreactivity in 2/6 and K562 reactivity in 0/4. W6/32 blocking and T3 modulation of cytotoxicity were almost invariably concordant against the same target. The data suggest that, to accomplish lysis of autologous and allogeneic tumour targets, certain clones require MHC recognition and a functional CD3 complex, while for others with similar target cell repertoires, there is no such requirement. It is possible that T-cell clones responding to a tumour-associated antigen (TAA) in the context of self MHC antigens can also respond to an allogeneic class-I product in the absence of TAA, and/or that aberrant class-I antigen expression on autologous tumours accounts for the alloreactivity.
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006680:HLA Antigens