HLA class I epitopes accounted for by single residues.

We examined the serological reaction of 50,000 HLA antisera for correlations with amino acid substitutions at 16 variable residues on the A locus and 8 variable residues on the B locus. We identified antisera that produced mutually exclusive allelic reactions corresponding to amino acid variants at the various residues. We assumed that by this procedure, epitopes that were determined by a single amino acid substitution could be identified. Among 55 variable residues on the A locus, antibodies that reacted in an allelic fashion were found for 16, or 32%. These serologically determined epitopes were on the alpha helix for 13 of the 16 residues, and 3 were in the beta sheet. Among 54 variable residues for the B locus, antibodies were found to 8 which reacted in a mutually exclusive pattern. Thus, 13% of the residues were serologically defined. Sixteen "monospecific" HLA specificities were determined by a single residue. Interestingly, many "multispecific" sera could be accounted for by reactions to a single amino-acid defined epitope. We assume that most of the other monospecific and multispecific specificities are determined by conformational epitopes, as described in an accompanying article (Ch. 33).