CROSS-REACTIVITY AMONG THE PRODUCTS OF 3 NONALLELIC H-2 LOCI, H-2LD, H-2DQ, AND H-2KK

Cross-reactions of the products of three nonallelic loci, H-2K, H-2D, and , have been studied by serological, immunochemical, and cellular immune techniques. Immunoprecipitation experiments revealed a determinant shared between L and D molecules but absent on D molecules. By cytotoxic screening of sera from individual mice an exceptional anti-L serum was found which cross-reacted with an H-2 antigen. Genetic mapping studies suggested that the basis of this activity was an L serological cross-reaction. Cytotoxic T cells generated to L alloantigens were also found to recognize a cross-reacting 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.The major transplantation antigens are cell surface glycoproteins which were originally recognized because of their predominant role in determining the fate of allografts. Their natural function remains unclear, although they have recently been shown to be involved in several immunological phenomena such as host response to chemically modified or virus-infected syngeneic cells. Murine major transplantation antigens, H-2 antigens, are encoded by genes that are located in two separate but tightly linked chromosomal segments, the and regions. The first evidence that the products of the and regions were structurally homologous was that certain alloantisera to the antigens encoded in one region serologically cross-reacted with products of the alternative region cf. These observations inspired the two-loci or gene duplication model for the H-2 antigens of the murine major histocompatibility complex .Data obtained using cocapping on the cell surface , immunoprecipitation , and partial amino acid sequences are all consistent with the region containing a single locus determining only one product, K. However, recent cocapping and sequential precipitation experiments have demonstrated that the region contains at least two loci, and encoding the 45,000-mol wt glycoproteins D and L, respectively. The L molecules were detected in haplotypes and because they did not bear private specificities but did react with certain alloantisera to public specificities. This finding may imply that is not as polymorphic as and and may also indicate that L is structurally dissimilar from K and D. By analogy to the cross-reactions observed between K and D, detection of common determinants shared between L and either K or D would support the hypothesis that all three loci originated from a common primordial gene. We investigate here cross-reactions between products and or products using serological techniques and T cell cytotoxicity studies. © 1979 by The Williams and Wilkins Co.