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A novel role for MHC class II antigens: evidence implicating a protective effect on tumour cells against cytotoxicity by NK and LAK cells.

There are several lines of evidence clearly demonstrating that major histocompatibility complex (MHC) class I antigens are important in protecting haemopoietic tumour cells from natural killer (NK)-mediated cell lysis. In the present studies we examined the role of MHC class II antigens in affording such protection to haemopoietic tumour cell lines. NK and lymphokine-activated killer (LAK) lysis were performed on two human B lymphoma cell lines and their mutants lacking HLA class II expression, i.e. DR, DP and DQ. Raji and T5-1 were compared to their mutants RM3 and 6.1.6, respectively. Significantly more lysis was observed with the mutants compared to the parent cell line. Effectors used included (1) peripheral blood NK effectors, (2) a human NK cell line (NK 3.3), and (3) peripheral blood LAK effectors. The increased lysis with the mutants could not be explained on the basis of (1) increased conjugate formation, (2) increased cell fragility or (3) ineffectual expression of HLA class I and other non-HLA antigens. These findings suggest that HLA class II molecules may have a novel role. They may be relevant not only in antigen presentation but may also protect tumour cells (and possibly normal activated lymphoid cells) against lysis mediated by NK and LAK cells.