Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation

Abstract

Major histocompatibility complex (MHC) class I molecules can function as specific target antigens in T-cell-mediated cytotoxity. In addition, T cells can kill target cells through non-MHC antigens, for example, virally infected cells, if the target and effector cells express the same MHC class I antigens. Consequently, quantitative and/or qualitative variations in the expression of the H-2/HLA antigens on the target cells could interfere with MHC-restricted immune reactions. We have reported that the AKR leukaemia cell line K36.16, a subline of K36 (ref. 3), on which the H-2Kk antigen cannot be detected, is resistant to T-cell lysis and grows very easily in AKR mice. Other AKR tumour cell lines, like 369, which have a relatively large amount of H-2Kk on their surface, are easily killed by T cells in vitro and require a much larger inoculum to grow in vivo. Monoclonal antibodies against H-2Kk, but not against H-2Dk, prevented the killing by T cells. This suggests that some tumour cells grow in vivo because tumour-associated antigen(s) cannot be recognized efficiently by the host's immune system, due to the absence of MHC molecules which would function as restriction elements for T-cell cytotoxicity. We have tested this hypothesis by introducing the H-2Kk gene into the H-2Kk-deficient AKR tumour cell line K36.16 and have now demonstrated directly the biological relevance of H-2Kk antigen expression in the regulation of the in vivo growth of this tumour cell line.

Cytotoxic T lymphocytes (CTL) against a transforming gene product select for transformed cells with point mutations within sequences encoding CTL recognition epitopes.

“…Tumor cell variants that escape CTL immunosurveiUance have been described (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). In most instances, the emergence of CTL escape variant cells is associated with the decrease or absence of MHC class I antigens required for antigen recognition by CTL (11)(12)(13)(14)(15)(16). In other cases, a complete loss of tumor antigen from the variants has been reported (6,10,(17)(18)(19).…”

Expression of B7.1 (CD80) in a renal cell carcinoma line allows expansion of tumor-associated cytotoxic T lymphocytes in the presence of an alloresponse

“…Animal tumor models suggest, however, that allogeneic responses may actually enhance the development of tumor protection against syngeneic tumors in vivo. [2][3][4][5][6] Furthermore, it was shown that an allogeneic response supported the generation of tumor-antigen specific T cells that were capable of eliminating established metastases in a murine model. 6,7 In order to assess the feasibility of using an allogeneic strategy for vaccination of patients with metastatic RCC, that proliferated over extended periods of time in mixed lymphocyte tumor cell (MLTC) cultures.…”

Instability of expression of major histocompatibility antigens in fibroblasts expressing activated ras oncogene: constitutive and interferon-gamma induced class I and class II antigens in a series of clonal isolates of murine fibroblasts transformed by v-Ki-ras

“…This is reflected in the finding, for example, that transfecting MHC antigen genes into an MHC antigen negative tumour line (so that it becomes antigen positive) drastically reduces its tumorigenicity (Hui et al, 1984;Tanaka et al, 1985;Wallich et al, 1985). The implication of this is that the T cell branch of the immune system is in somne way important in the control of tumour growth, although it is of course possible that some other feature of MHC antigen biology may be involved.…”