Molecular diversity of the HLA-C locus in unrelated marrow transplantation

The diversity of HLA-C exon-2 alleles in 56 HLA-A, B, DRB and DQB1-matched patient-unrelated marrow donor pairs was examined by non-cloning polymerase chain reaction-based sequencing of genomic DNA. This method allows simultaneous analysis of both alleles in heterozygous samples. All Cw5-positive individuals encoded a sequence which differed from the published Cw*0501 sequence at position 61. Among 82 samples assigned a single antigen by serologic testing, 64 (78%) were heterozygous for two distinct alleles when tested by sequencing. Cw*1202, 1601 and 15 were identified in samples for which no phenotype could be assigned (C "blank"). Finally, 7 of the 56 HLA-A, B, DRB, DQB1-matched pairs (12.5%) were mismatched for one or both HLA-C alleles. We conclude that sequence-based methods constitute the optimal strategies for typing HLA-C alleles in the unrelated marrow transplant population.