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

Abstract

The H-2L dm1 and H-2D dm1 MHC antigens of the B10.D2 ( H-2 dm1 ) mutant mouse strain (formerly known as M504 or H-2 da ) have been compared to the H-2L d and H-2D d antigens of the B10.D2 ( H-2 d ) mouse strain. L dm1 and L d are 45 000 M r 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 D dm1 and D d 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 L dm1 and L d is 80 percent. A newly defined antigen (M r = 39 000), designated gp39 dm1 , was found in glycoprotein extracts of the dm1 strain but not of the d strain. This antigen coprecipitates with L dm1 but does not coprecipitate with D dm1 indicating that it lacks the H-2.4 determinant. In comparison with L dm1 , gp39 dm1 appears to contain far fewer Arg and Lys residues and is most likely not a simple proteolytic fragment of L dm1 . Finally, peptide maps of the D dm1 antigen show that the majority of its Arg peptides are identical to D d Arg peptides, whereas at least five of its Lys peptides and three of its Arg peptides correspond not to D d peptides but to L d and L dm1 peptides. These data raise the possibility that the D dm1 antigen is a hybrid molecule and they have also revealed an unexpected level of complexity in the dm1 mutant phenotype.