The HLA-DRw8 lineage was generated by a deletion in the DR B region followed by first domain diversification.
Sequences were generated for the first, second, and 3'UT regions of DRw8 beta-chain genes from two cell lines differing in their T cell determined allospecificities. Both have second domain sequences homologous to the B1 locus of the DRw52 family (DR3, DR5, and DRw6) and not the B3 locus. However, the 3'UT sequence is homologous to the 3'UT region of the B3 locus of the DRw52 family, and not the B1 locus. The first domain sequences are B1-like as opposed to B3-like and show polymorphism in the region encoding the putative alpha-helical region of the DR beta-chain. The easiest interpretation is that the DRw8 haplotypes constitute a sublineage within the DRw52 group and that this lineage has arisen by a small chromosomal deletion of the region between the B1 locus and the B3 locus. This deletion included the 3'UT region of the B1 locus, the B2 pseudogene, and the 5' end of the B3 locus including the exons encoding the first and second domains. After the deletion, two changes in the first domain arose by a mutational mechanism, possibly gene conversion. One of these changes parallels one seen in the DRw11 lineage.
Gorski
J
J
Immunogenetics Research Section, Blood Center of Southeastern Wisconsin, Milwaukee 53233.
D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D002872:Chromosome Deletion; D005796:Genes; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000032:analysis / Q000502:physiology
D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C051104:HLA-DR52 antigen; C041559:HLA-DR8 antigen