HLAMATCHMAKER-BASED DETERMINATION OF HLA-DR AND HLA-DQ COMPATIBILITY AT THE STRUCTURAL LEVEL.

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HLAMATCHMAKER-BASED DETERMINATION OF HLA-DR AND HLA-DQ COMPATIBILITY AT THE STRUCTURAL LEVEL.
Medhat Z. Askar, MD PhD and Rene J. Duquesnoy, PhD . Pittsburgh PA, University of Pittsburgh Medical Center, 15261, Transplant Pathology .

This is the first report on the HLAMatchmaker algorithm to determine DR and DQ compatibility at the structural level. The class II version is similar to the program for class I compatibility in that it considers amino acid triplet polymorphisms as potential epitopes and matching is done by intralocus and interlocus comparisons. Since the serological determination of class II antigens is often unreliable, this algorithm considers only DNA-typing results and uses allelic subtypes of class II antigens. In the HLA-DR region, there is considerable sequence homology between DRB1, DRB3, DRB4 and DRB5 molecules. Because of these overall similarities in molecular structure, HLAMatchmaker can incorporate interlocus comparisons between DRB triplets. On the other hand, sequence analysis shows many monomorphic residue differences between DQB and DRB molecules. This means that DQB1 triplet matching cannot incorporate interlocus comparisons with DRB alleles and vice versa. The program considers 95 triplets in 15 DRB positions and 51 triplets in 13 DQB positions in the membrane-distal domains. It can readily determine which class II antigen and allele is zero-triplet mismatched and donor-recipient compatibility can be determined at the triplet level in both directions. We have applied an HLAMatchmaker-based serum version to analyze the class II ELISA serum data. High PRA sera have antibodies against class II triplets shared between DRB1 or DQB1 antigens and/or alleles similar to the cross-reacting groups of class I antigens sharing a defined triplet. This program permits the identification of acceptable and unacceptable class II mismatches for sensitized patients.
The Class II version of HLAMatchmaker and its corresponding serum analysis program can be downloaded from the Internet website: http//tpis.upmc.edu.