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Immunogenetic Analysis of H-2 Mutations

III. Genetic Mapping and Involvement in Immune Reactions of the H-2^Ka Mutation¹

Jan Klein², James Forman², Vra Hauptfeld² and Igor K. Egorov³

From the Department of Microbiology, The University of Texas Southwestern Medical School, Dallas, Texas 75235 and the Institute of General Genetics, U.S.S.R. Academy of Sciences, Moscow 117312, U.S.S.R.

Abstract

Mutation M523 (H-2^ka) occurred spontaneously in strain CBA/CaLacSto and was discovered during routine skin graft testing for genetic homogeneity. By linkage and complementation tests, the mutation was previously mapped in the K end of the H-2 complex. We demonstrate that the mutation occurred in the K region, without affecting the I region in the K end of the complex. The mutant antigens cause rejection of skin grafts, stimulate cells in mixed lymphocyte culture, and function as stimulators as well as targets in cell-mediated lymphocytotoxicity. Yet, they are serologically indistinguishable from the antigens of the original strain and do not induce formation of humoral antibodies upon immunization of the CBA strain. Together with the results obtained on testing of other H-2 mutants, the data strongly support the notion that classical H-2 antigens (i.e., products of the H-2K and H-2D loci) can function as lymphocyte-stimulating determinants, and that I-region differences are not required for the induction of strong cell-mediated lymphocytotoxicity.

Footnotes

¹ This research was supported by grants AI11851, AI11850 and AI11879 from the National Institutes of Health.

² Department of Microbiology, The University of Texas Southwestern Medical School, Dallas, Texas 75235.

³ Institute of General Genetics, U.S.S.R. Academy of Sciences, Moscow 117312, U.S.S.R.