Complete characterization and sequence of an HLA class II DRβ chain cDNA from the DR5 haplotype

The human major histocompatibility complex includes the DP, DQ, and DR subregions, each of which contains at least one α chain gene and two β chain genes. The products of the α chain gene and a β chain gene from a given subregion combine to form a heterodimer which is found predominantly on the surface of immunocompetent cells, and is essential for effective cell-cell interactions and the generation of an immune response. The β chain of the DR molecule is highly polymorphic, and it is this polymorphism which is thought to be ultimately responsible for the specific immune responsiveness and disease predisposition conferred by different DR molecules. While the sequences of DRβ chains of the homozygous DR1 cells, homozygous DR2, homozygous DR4, DR3/w6 cells and DR4/w6 genotypes have been partially or completely characterized, no sequence is yet available for the DRβ chain from a homozygous DR5 cell. A cDNA library was therefore constructed from the Swei cell line homozygous for the DR5 haplotype. A β chain clone was isolated, characterized, and sequenced. Comparison with previously published DRβ chain restriction endonuclease maps and nucleotide sequences demonstrated that this clone was a DRβ chain clone. Comparison of the deduced amino acid sequence with other DRβ chain amino acid sequences shows three regions of variability in the first external domain, corresponding to amino acid residues 9-13, 26-38, and 67-74. The sequence of each of these variable regions in the β chain from DR5 cells was identical or nearly identical to the sequences of variable regions found in the β chains of other DR haplotypes, supporting the notion of gene conversion as an evolutionary mechanism generating polymorphism. The second external domain, and transmembrane and intracytoplasmic regions show a high degree of sequence conservation.