Comparison of structural and functional variation in class I HLA molecules: the role of charged amino acid substitutions.
Functional and structural heterogeneity of HLA class I molecules was sought among five donors serologically identical for A2, A3, B7, and Bw44. Functional differences were identified by cell-mediated lympholysis (CML) after allogeneic mixed lymphocyte reaction among the five donors. Structural differences were characterized by high resolution two-dimensional electrophoretic maps of the class I HLA proteins synthesized by peripheral blood lymphocytes of these donors. Cells from three donors showed no CML-defined differences from one another; their HLA protein maps were identical. The cells of one donor recognized an A3-associated target antigen on the cells of all the other donors; her HLA map revealed a unique protein with altered isoelectric point. Another donor's cells differed by two CML-detected antigens: one was identified as a variant of Bw44 ("44.2") and the other was associated with Cw4. This donor's two-dimensional HLA map showed two novel charged proteins. By using these data, a two-dimensional map locating HLA-A2, -A3, -A3', -B7, -Bw44.1, -Bw44.2, and -Cw4 was prepared. Because each of three CML-detected antigens was correlated with a protein of distinctive charge, our results and the available published data raise the possibility that amino acid substitution producing charge variation may be a particularly important mechanism in the generation of CML-detectable HLA diversity.
D000596:Amino Acids / Q000032:analysis*; D000937:Antigen-Antibody Reactions; D055598:Chemical Phenomena; D011232:Chemical Precipitation; D002621:Chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000032:analysis; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D010455:Peptides / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000596:Amino Acids; D000939:Epitopes; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D010455:Peptides