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HLA amino acid residue matching.

1. HLA amino acid sequences have been defined for 77 A- and 176 B-locus antigens. Amino acid polymorphisms occurred at 80 A- and 74 B- sequence positions. 2. The majority of amino acid substitutions occurred in regions involved with peptide binding. A surprisingly large number of substitutions were in the alpha-3 regions of the molecule. 3. Graft outcome in cadaveric and living donor transplants was calculated for mismatches for every possible amino acid allele. 4. Two-thirds of the HLA-A and -B locus antigens used for solid organ allocation had disparate frequencies in White and Black recipients. Only 6 antigens were found in over 20% of White recipients. 5. Five-year survival for first transplants was 66% for zero-DR, zero-residue mismatched kidneys compared to 59% for kidneys with mismatches. Half-life for residue matched kidneys was 11 years compared with 8 years for kidneys with mismatches. 6. Mismatches for all of the A-locus residues and the majority of B-locus residues were correlated with positive crossmatches. 7. None of the crossmatches for highly sensitized patients with zero-A,B,DR mismatches were positive; 30% of zero-residue mismatched patients had a positive crossmatch compared to 70% of cases with mismatches.