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The GIX antigen expressed on the thymocytes of GIX+ mice is a type-specific constituent of glycoprotein gp70, which forms the major envelope component of murine leukemia virus. In the prototype GIX+ mouse strain 129, this glycoprotein is a Mendelian character expressed independently of virus production. In the intact thymocyte plasma membrane, part of this glycoprotein, bearing group-specific (gs) antigen, is inaccessible to antibody. The moiety bearing the type-specific GIX determinant is accessible to GIX antibody, which may be an important factor in determining the consequences of autoimmune responses involving GIX. Previously, all attempts to induce GIX antibody in mice had failed. We now find that the hybrid mouse (B6-GIX+ X 129) spontaneously produces substantial amounts of GIX antibody, presumably of the IgM class appearing as early as 2 mo of age. The specificity of the GIX natural mouse antibody is the same as that recognized by the conventional GIX typing serum produced in rats ("anti-NTD"). As neither parent strain produces appreciable GIX antibody, we surmise that this autoimmune response requires two dominant genes, each parent contributing a high-response allele to the hybrid. These can be envisaged as two immune response loci, controlling different immunocompetent cells which must cooperate to produce GIX antibody. Production of GIX antibody by the hybrids increases progressively with age. This is accompanied by decreased expression of GIX antigen on their thymocytes. We attribute this to antigenic modulation. Antibody to gs antigen of gp70 is also found in autoimmune (B6-GIX+ X 129) hybrids but not in either parent strain. We are investigating evidence of a pathological autoimmune syndrome in these hybrids. The special interest of this syndrome is that it presumably signifies the consequences of autoimmunization to a single C-type virus component, expressed without significant virus production, in a mouse with no evident genetic predisposition to such disease in the absence of that antigen.

Spontaneous autoimmunization to GIX cell surface antigen in hybrid mice.