The H-2 and Ia antigenic composition of strain pairs B10.D2 (H-2d) and M504 (H-2da), A.CA (H-2f) and M506 (H-2fa), and CBA (H-2k) and M523 (H-2ka) was compared by testing their cells against a battery of oligospecific antisera, by performing absorption analysis, and by cross-immunization. The two strains of each pair are congenric and differ in that the second strain of the pair carries a mutation that occurred in the H-2 haplotype of the first strain. The Ia composition of each mutant haplotype was found to be the same as that of the haplotype from which the mutant was derived. Several differences in the serologically detectable H-2 antigens were found. The H-2d and H-2da haplotypes were found to differ in that the latter lost at least one and gained another antigen. The affected antigens were demonstrated to be classic H-2 antigens controlled by the H-2D locus. The H-2f and H-2fa haplotypes were found to differ in that antigens 26, 37, and 39, controlled by the latter, bound their respective antibodies less firmly than those controlled by the former haplotype. Since all three antigens are coded for by the H-2K locus, since no change was found in the D-region controlled antigens, and since the H-2fa mutation maps in the K end, we conclude that most likely the mutation occurred in the K region. The H-2k and H-2ka haplotypes were found to differ in that the latter lost one antigen encoded by the H-2Kk allele. This mutation, therefore, must have occurred in the H-2K locus. The data tip the scale of evidence in favor of the interpretation that each of the H-2 mutations occurred in a single region, either K or D. No evidence for a second mutation within any of the other H-2 regions was found.
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