Unexpected complexity of the dm1 mutation revealed in the structure of three H-2D/L-related antigens.

The H-2L-dm1 and H-2Ddm1 MHC antigens of the B10.D2 (H-2dm1) mutant mouse strain (formerly known as M504 or H-2da) have been compared to the H-2Ld and H-2Dd antigens of the B10.D2 (H-2d)mouse strain. Ldml and Ld are 45 000 Mr antigens and both are reactive with anti-H-2."28" (k/r anti-h2) serum and unreactive with anti-H-2.4 (k/b anti-a) serum which detects private determinants of the Ddm1 and Dd antigens. However, the tryptic peptide compositions of these two antigens are different and, based on the number of major tryptic peptides which coelute during ion-exchange chromatography, the estimated peptide homology between Ldm1 and Ld is 80 percent. A newly defined antigen (mr = 39 000), designated gp39dm1, was found in glycoprotein extracts of the dm1 strain but not of the d strain. This antigen coprecipitates with Ldm1 but does not coprecipitate with Ddm1 indicating that it lacks the H-2.4 determinant. In comparison with Ldm1, gp39dm1 appears to contain far fewer Arg and Lys residues and is most likely not a simple proteolytic fragment of Ldm1. Finally, peptide maps of the Ddm1 antigen show that the majority of its Arg peptides are identical to Dd Arg peptides, whereas at least five of its Lys peptides and three of its Arg peptides correspond not to Dd peptides but to Ld and Ldm1 peptides. These data raise the possibility that the Ddm1 antigen is a hybrid molecule and they have also revealed an unexpected level of complexity in the dm1 mutant phenotype.