AN APPARENT FUNCTIONAL CORRELATION BETWEEN VARIATIONS IN AMINO-ACID-RESIDUES IN HLA-DR4.1 AND 4.2 SEROLOGICAL SUBTYPES AND OLIGONUCLEOTIDE CHARACTERIZATION

HLA-DR4 can be subdivided serologically into two specificities, DR4.1 and DR4.2, using well-defined monospecific alloantisera used in the 11 th International Histocompatibility Workshop, In this study, a total o f 1095 random DR4-positive individuals from several ethnic groups were tested first for serotype DR4.1/4.2 and then for DRB104 alleles usin g polymerase chain reaction (PCR) followed by sequence-specific oligon ucleotide probe hybridization (SSOPH). An almost 100% correlation betw een samples testing positive for DR4.1 and the presence of alanine at position 74 was observed, while samples testing positive for DR4.2 cor related with the presence of glutamic acid at position 74. DRB104 all eles 0401, 0402, 0404, 0405, 0408, 0409 and 0410 are aligned in functi onal groups which coincide with the serological subtype of DR4.1. DRB1 04 alleles 0403, 0406, 0407 and 0411 coincide with subtype DR4.2. Ami no acid substitutions at positions 57, 71 and 86 indicate other signif icant variations between alleles within the serological subgroup of DR 4.1 and define five minor subgroups. The serologic and oligonucleotide allelic subgroups are in turn correlated with recognized cellular Dw antigens. While sequence data provide evidence of structural differenc es, data on cellular antigens support a functional association between these designated groups and their significance in transplantation and GVHD. Testing results are categorized by ethnic group in order to est ablish frequency data for donor selection criteria.