Gene organization of DC and DX subregions of the human major histocompatibility complex.

Abstract

The DC and DX subregions of the human major histocompatibility complex (MHC) were cloned from a cosmid library made from a human B-cell line, Priess. The DC subregion, 48 kilobases, includes the DC.alpha. and DC.beta. genes. A 2nd DC-like region, the DX subregion, 35 kilobases, contains the DX.alpha. gene and a newly found .beta. gene termed DX.beta.. Since the DC and DX genes are highly homologous in nucleotide sequence, gene size, exon-intron organization and direction of transcription, the DC and DX subregions were presumably generated by duplication of an ancestral .alpha.-.beta. gene pair. Nucleotide sequencing indicates that all 4 genes have intact coding sequences and promoter regions. Homology between the upstream promoter sequences of these 4 genes and 7 other class II genes at nucleotides -69 to -78 and -98 to -110 highlights these previously described conserved elements. A striking conservation of flanking .alpha.-gene-specific and .beta.-gene-specific sequences was observed. Comparison of Southern blots of Priess DNA with DC.alpha. and DC.beta. c[complementary]DNA probes with isolated cosmid clones showed that the human chromosome encodes only 2 DC.alpha.-related and 2 DC.beta.-related genes, namely, DC.alpha., DX.alpha., DC.beta. and DX.beta., and the DC and DX subregions are homozygous in Priess cells.