Association of high sensitization to the structure of HLA class I alleles

Some HLA Class I alleles or groups of alleles can be explained by exclusive residues which may explain their structural uniqueness. However, many sera are directed to alleles whose structural uniqueness is explained only by a combination of nonexclusive residues. A program implementing a combinatorial search algorithm was developed to analyze serological data by associating the primary structure of specific alleles to reaction patterns of broad multispecific sera. The method determines the residue or residues whose associated alleles best describe the serum specificity. The raw data reaction patterns direct the search, which utilizes known primary sequence information of HLA Class I alleles. Three-hundred highly positive sera from parous females were analyzed; 74 were highly correlated to the A locus and 125 to the B locus. Some of the remaining sera were associated with multiple loci. Reorganization methods were applied to the data. Clusters of residues associated with certain alleles focus attention on specific locations on the HLA Class I molecule. These regions may be included in, or in close proximity to, the serological determinant. Serological descriptions of certain broad specific sera have been termed "public epitopes." Specificities associated with distinct conserved regions of the Class I molecule offer a molecular basis for many public epitopes. Similar reaction patterns to 3 serologically allelic regions were found in pregnancy allosera, monoclonal antibodies, and transplant recipient sera. The correlated areas were: positions 166 and 167 of the alpha 2 domain alpha helix on the A locus, positions 79-83 of the alpha 1 domain alpha helix on the A locus, and positions 80-83 on the A and B loci.