A cellular and functional split in the DRw8 haplotype is due to a single amino acid replacement (DR ? ser 57- asp 57 )

Abstract

The single DR beta chain gene of the DRw8 haplotype has been suggested to carry both the DRw8 and the DRw52 epitopes. Cellular typing has shown that the DRw8 haplotype can be split into three subtypes, Dw8.1. Dw8.2, and Dw8.3, presumably due to a polymorphism in the DRw8 _β chain. Furthermore, Dw8.1 and Dw8.2 cells present influenza virus antigen to different T-cell clones. In the present study, DRw8/Dw8.2 β chain cDNA was cloned and characterized. A comparison of this sequence with a partial DRw8/Dw8.1 β chain gene suggested that the DRw8 split is due to a single amino acid replacement of ser ₅₇ -asp ₅₇ caused by three nucleotide substitutions in the same codon. In most DR haplotypes, two expressed DR beta chain genes exist. Comparing the nucleotide sequence of the single beta gene in the DRw8 haplotype to those of other DR beta genes revealed that the DRw8 beta gene sequence is most closely related to the DRBI genes of the DR3, 5, and w6 haplotypes. However, the comparisons also showed that it was not possible from sequence similarities to divide the DR beta genes into two or more distinct allelic series.