HLAMatchmaker: a molecularly based algorithm for histocompatibility determination. I. Description of the algorithm

Abstract

This report describes an algorithm for identifying acceptable HLA antigens for highly alloimmunized patients without the need for extensive serum screening. This algorithm is based on the concept that immunogenic epitopes are represented by amino acid triplets on exposed parts of protein sequences of human leukocyte antigen chains (HLA-A, HLA-B, and HLA-C) accessible to alloantibodies. A computer program (HLAMatchmaker) has been developed to determine class I HLA compatibility at the molecular level. It makes intralocus and interlocus comparisons of polymorphic triplets in sequence positions to determine the spectrum of non-shared triplets on donor HLA antigens. In most cases is it possible to identify certain mismatched HLA antigens that share all their polymorphic triplets with the patient's HLA antigens and could therefore, be considered fully compatible. HLAMatchmaker permits also the identification of additional mismatches that are acceptable as determined from the triplet information on HLA-typed panel cells that do not react with patient's serum.HLAMatchmaker provides an assessment of donor-recipient HLA compatibility at the structural level and this algorithm is different from conventional methods based on the mere counting of numbers of mismatched HLA antigens or CREGs. This donor selection strategy is suitable especially for allosensitized patients in need of a compatible transplant or platelet transfusion.