Lymphocytotoxic antibodies produced by H—2 allo-immunisation distinguish between MuLV-positive and -negative substrains of the same H-2 haplotype

Abstract

In C57BL mice of certain H–2 types, such as B10.A (H–2^a), ecotropic leukemia virus has been shown to be transmitted by milk-borne infection. By selecting virus-positive and virus-negative B10.A mothers and foster-nursing the B10 (H–2^b) newborn animals, four sub-lines of C57BL/10 mice have been obtained—B10.A V⁺, B10.A V⁻, B10 V⁺ and B10 V⁻ (see Fig. 1 and ref. 1). Milk transmission of naturally prevalent B-tropic virus (V⁺ sub-lines) leads to a persistent infection of all the offspring over more than 8 generations². We have studied the consequences of this kind of virus infection on the expression and immunogenicity of antigens coded for by the H–2 complex. This complex exerts a marked influence on oncogenesis by a variety of oncogenic RNA viruses^3,4. The H–2K and H–2D loci restrict the specificity of virus-specific cytotoxic T lymphocytes⁵. In some instances, a direct physical association between H–2 and viral antigens has been demonstrated^6–10. In our work, groups of B10.A V⁺ and B10.A V⁻ mice were immunised with B10V⁺ and B10 V⁻ lymphoid cells. Production of anti-H–2^b antibodies was expected and observed in these sera. However, surprisingly, in the combination of B10 V⁺ donor and B10.A V⁻ recipient, after prolonged hyperimmunisation, We obtained sera that reacted positively in the routine microlymphocytotoxicity test with B10.A V⁺ lymph-node cells, but not with B10.A V⁻ cells. B10V⁻ cells were able to absorb this antibody. Our preliminary conclusion is that the milk-transmitted virus, soon after birth, introduces a serologically detectable antigen which is recognised in association with H–2. The prerequisite for the formation of this kind of antibody is the immunisation of H–2 haplotype-different V⁻ recipients with V⁺ donor cells.