CONTRASTING EFFECTS FROM A SINGLE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULE (H-2E) IN RECOVERY FROM FRIEND-VIRUS LEUKEMIA

Resistance to erythroleukemia induced by infection with the Friend vir us complex (FV) has been mapped to several genes residing both within and outside the murine major histocompatibility complex (MHC). MHC gen es located in the A, D, and Qa/Tla regions of the murine H-2 complex h ave been shown to affect disease resistance through their capacity to regulate various aspects of the host immune response to viral antigens . This study establishes H-2E as the fourth MHC locus controlling immu nological resistance to FV. Our investigation into the role of H-2E mo lecules revealed two distinct and opposite effects on recovery from Fr iend disease. H-2(b/b) mice normally lack a functional E gene product and are resistant to high doses of FV. The expression of H-2E molecule s in H-2 recombinant or transgenic mice of this genotype resulted in a significant decrease in spontaneous recovery from FV-induced leukemia . In contrast, H-2E expression also appeared to influence recovery fro m Friend disease in a positive manner, since blocking these molecules with anti-E antibodies in vivo significantly decreased recovery from F riend disease. The data indicate that the positive effects of H-2E mol ecules derive from their function as restriction elements for helper T -cell recognition of the viral envelope glycoprotein, and eve postulat e that the negative effects are due to H-2E-dependent deletions in the T-cell repertoire during development.