Reduced humoral and cellular cytotoxic sensitivity in major histocompatibility variants of the YAC (Moloney) lymphoma

Previously we have reported that two sublines of the YAC lymphoma selected for reduced expression of H-2^a and Moloney-virus determined cell-surface (MCSA) antigens are, in contrast to YAC, allotransplantable in H-2-incompatible recipients, and resistant to rejection by preimmunized semisyngeneic hosts. A third YAC variant with reduced MCSA but unchanged H-2-antigen expression, was not allotransplantable and showed only a slight decrease in its immunosensitivity in preimmunized semisyngeneic hosts in vivo. This suggested that H-2-antigen expression may be more important than MCSA expression for recognition and rejection by semisyngeneic mice. We have now tested the sublines expressing low H-2^a for their in vitro sensitivity to humoral and cell-mediated lysis. — The variants were more resistant than YAC to complement lysis by anti-H-2^a, anti-MCSA, anti-Thy 1.2 and antispecies sera. Absorption tests with antispecies serum indicated that the decreased cytolytic sensitivity of the variants was not related to the concentration of the relevant antigens, which was similar to that of the original YAC tumor. As expected from the low amount of H-2^a the variants showed a decreased sensitivity to the killing effect of allogeneic cytotoxic T lymphocytes (CTL). They were also lysed to a lesser extent than YAC by semisyngeneic CTL, probably directed against virally determined antigens. However, they were also less sensitive to lysis by natural killer (NK) cells, although NK lysis is probably unrelated to MHC expression. In conclusion, our selection for reduced H-2-expression appears to have resulted in the isolation of variants with a generally increased resistance to various humoral and cell-mediated lytic functions.On leave from Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas, Venezuela.