HLA epitopes detected by serology.

There is evidence that many of the so-called multispecific cytotoxic antisera react to the amino acid-defined epitopes of the HLA-A and B loci molecules. This evidence is based on the finding that a group of sera produced allelic reactions which corresponded to amino acid substitutions. Antisera for 29 amino acid variants were identified at 67 variable residues on the A locus and for 17 of the 51 variable sites on the B locus. The results were validated by showing that the reactions produced by testing cells from 111 individuals on an epitope typing tray fit the Hardy Weinberg equilibrium. This means that the alleles defined by the antisera behaved as alleles in the random population. Tests of homozygous cells on the epitope typing trays produced completely mutually exclusive reaction patterns as expected on the basis of the amino acid substitutions. Two examples are cited in which immunization across a single HLA "antigen" difference existed between donor and recipient, resulting in a "multispecific" antiserum. The specificities contained in the serum exactly fit an amino acid difference between the donor and recipient.