HLA epitope matching. Contribution of matched residues to epitopes recognized by alloantibodies.

Applying absorption-elution techniques with homozygous typing cells and flow cytometry, a number of alloantibodies that recognized HLA-B62 but not B46 were identified. B62 and B46 are identical except in amino acids 66-76, which are probably recognized by the B62-specific antibodies. The patients who made these antibodies, however, had HLA antigens sharing amino acids 66-76 with B62, indicating that residues that are identical to the patient's own contribute to the antigenic determinants of foreign HLA molecules. Fine specificity analysis of most of these antibodies revealed that they recognized residues in the 66-76 segment in addition to other residues which were located in close proximity to this segment. We conclude that mismatched amino acid residues located in one part of the HLA molecule can interact with residues that are not different from those in the patient's own HLA molecules to form epitopes recognizable by alloantibodies. These findings should be helpful in improving our understanding of how to use current knowledge at the molecular level for the purpose of matching transplant donors and recipients.