Quantitative variations in the expression of H-2 antigens on murine leukemia virus-induced tumor cells can affect the H-2 restriction patterns of tumor-specific cytolytic T lymphocytes.

Comparative quantitative experiments were designed to study the expression of H-2Kd and H-2Dd antigens on three different leukemia cell lines induced by Gross murine leukemia virus (MuLV)in BALB/c (H-2d) mice. The H-2 restriction patterns of syngeneic cytolytic T lymphocytes (CTL) directed against Gross MuLV-induced tumors were correlated with these quantitations of H-2Kd and H-2Dd antigens, Our results obtained by quantitative absorption of monospecific antisera indicated that the three BALB/c tumor cell lines expressed different amounts of H-2Kd and H-2Dd antigens, with H-2Dd antigen showing the greatest variability in expression because it ranged from barely detectable levels to one-eighth the amount of H-2Dd antigen expressed on normal BALB/c spleen cells. The H-2 restriction patterns of Gross MuLV-specific CTL were directly affected by these quantitative modulations in the expression of H-2Kd and H-2Dd antigens, as revealed by three independent approaches: (a) inhibition of CTL activity by monospecific anti-H-2 sera in the absence of complement; (b)competitive inhibition of CTL-mediated cytotoxicity by the addition of excess tumor cells into the reaction mixture; and (c) analysis of CTL specificities using cloned CTL populations. Our results thus indicate that H-2 restriction of tumor-specific CTL activity can be directed at the target cell level by variations in the expression of H-2 antigens.