Previous experiments defining the H-2 restriction element specificity of T cells responsive to F-MuLV envelope glycoproteins revealed that mAbs directed against I-Ab and, to a lesser extent, I-Ek inhibit in vitro proliferative responses. To further analyze the possible role of H-2 I-E gene products in immunity to Friend virus induced leukemia, animals infected with the Friend virus complex (F-MuLV and spleen focus forming virus) were treated in vivo with mAbs directed against the alpha or beta chain of the I-E surface glycoprotein. Administration of anti-I-Ekalpha or anti-I-Ekbeta completely inhibited recovery from splenomegaly in (A.BY x B10.A)F1 mice, while treatment with anti-I-Ab was virtually without effect. Treatment with anti-I-E mAb is associated with complete suppression of the IgG neutralization response with no depression of neutralizing IgM titers. Anti-I-E mAb treated animals also display a reduced capacity to transfer protection to naive, virus infected recipients, indicating a paucity of Friend virus reactive cells in the spleen. I-E restricted T cells are specific for epitopes on the virus envelope rather than on core proteins as determined by inhibition of delayed type hypersensitivity responses in vaccinia-env versus vaccinia-gag immunized hosts. The mechanism of inhibition does not appear to involve active T cell suppression, however, as evidenced by the absence of any effects on recovery or DTH in immune recipients of splenocytes from treated donors. A role for I-E in recovery was supported by additional studies in highly resistant, I-E-(A.by x B10)F1 mice expressing or lacking and I-Ekalpha transgene. Animals expressing the transgene (which allows for surface expression of an I-E gene product through complementation with an endogenous Ebeta gene) consistently exhibit a 30% higher incidence of persistent splenomegaly and a 15% higher incidence of mortality as compared to transgene negative litter mates. A manuscript is currently in preparation to describe this observation.
