Abstract
Two-dimensional peptide mapping was used to study the polymorphism of DR antigens, membrane glycoproteins composed of two chains, alpha and beta, and encoded by the human major histocompatibility complex (MHC). Four DR antigens were purified by immunoabsorption from four human lymphoblastoid cell lines homozygous at the DR locus. After labeling with 125I, alpha and beta chains were separated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and digested with pepsin. Comparison of the peptide maps showed a marked degree of polymorphism among beta chains: only 43% of peptides were common to all four chains and 15-21% of the spots were unique to a given chain. By contrast, only a limited variability was observed among alpha chains. Homology was 75% for the four chains and the percentage of unique peptides was very low. DR7 did not possess even a single unique peptide. The limited variability among alpha chains and the lack of "private" peptides in one of them point to the conclusion that the beta chain is the unique carrier of the alloantigenic specificities. Higher homology within the known crossreactive groups was not observed, suggesting that the determinants responsible for crossreactivity are on different molecules. From a genetic point of view, because beta chains show allele-associated polymorphism, they are likely to be MHC encoded, whereas the minor differences among alpha chains do not allow a similar conclusion. The available data point to an analogy between these DR antigens and the mouse I-E/C antigens.