A NOVEL ROLE FOR MHC CLASS-II ANTIGENS - EVIDENCE IMPLICATING A PROTECTIVE EFFECT ON TUMOR-CELLS AGAINST CYTOTOXICITY BY NK AND LAK CELLS

There are several lines of evidence clearly demonstrating that major h istocompatibility complex (MHC) class I antigens are important in prot ecting haemopoietic tumour cells from natural killer (NK)-mediated cel l lysis. In the present studies we examined the role of MHC class II a ntigens 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 ex pression, i.e. DR, DP and DQ. Raji and T5-1 were compared to their mut ants RM3 and 6.1.6. respectively. Significantly more lysis was observe d with the mutants compared to the parent cell line. Effectors used in cluded (1) peripheral blood NK effecters, (2) a human NK cell line (NK 3.3), and (3) peripheral blood LAK effecters. The increased lysis wit h the mutants could not be explained on the basis of (1) increased con jugate formation, (2) increased cell fragility or (3) ineffectual expr ession of HLA class I and other non-HLA antigens. These findings sugge st that HLA class II molecules may have a novel role. They may be rele vant not only in antigen presentation but may also protect tumour cell s (and possibly normal activated lymphoid cells) against lysis mediate d by NK and LAK cells.