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

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Abstract
Major histocompatibility complex (MHC) class I molecules can function as specific target antigens in T-cell-mediated cytotoxity 1,2. 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 antigens2. 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 mice4. 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 vivo4. Monoclonal antibodies against H–2Kk, but not against H–2Dk, prevented the killing by T cells4,5. 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.