H-2D control of leukaemia susceptibility: mechanism and implications.

Genes in the D region of the murine major histocompatibility complex, H-2, confer resistance to radiation-induced leukaemia virus. H-2D gene control appears to ensue at a step subsequent to virus infection, since elimination of virus infected cells does not become apparent until 3--5 weeks after virus infection. Nonetheless, almost immediately after virus infection, expression of H-2D-coded antigens is markedly elevated on the surface of thymocytes from resistant (H-2Dd) but not susceptible mice (H-2Ds or H-2Dq). This increased H-2D antigen expression triggers a vigorous cell-mediated immune response which probably plays a key role in resistance to leukaemia via elimination of virus-infected cells. A hypothesis is put forth to explain the induction of increased sythesis and expression of H-2D antigens. This hypothesis postulates that the oncogenic segment of RadLV bears a close resemblance to H-2.4, the private specificity for H-2Dd, allowing it to integrate at or near the H-2Dd murine gene. Subsequent to integration, the rates of transcription and translation are altered with a resulting increase in cell surface antigen expression. Other possibilities are also discussed.