Cross-reactions of the products of three nonallelic H-2 loci, H-2K, H-2D, and H-2L, have been studied by serological, immunochemical, and cellular immune techniques. Immunoprecipitation experiments revealed a determinant shared between L(d) and D(d) molecules but absent on D(d) molecules. By cytotoxic screening of sera from individual mice an exceptional anti-L(d) serum was found which cross-reacted with an H-2(k) antigen. Genetic mapping studies suggested that the basis of this activity was an L(d)-K(k) serological cross-reaction. Cytotoxic T cells generated to L(d) alloantigens were also found to recognize a cross-reacting K(k) determinant. These studies therefore suggest that L, D, and K are three structurally homologous cell surface glycoproteins that have evolved from a common primordial gene.
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