Structure and nucleotide sequence of the heavy chain gene of HLA-DR.

Abstract

A 175-nucleotide-long primer extension product corresponding to the 5'' end of HLA-DR .alpha.-chain mRNA was used to isolate a genomic clone from a human DNA library. The entire HLA-DR.alpha. gene is contained in 2 contiguous EcoRI fragments spanning about 7.5 kilobases (kb); most of the sequence was determined. The 5'' end of the gene is contained in a 4.4-kb fragment, and the coding segments and the 3'' untranslated region are contained in a 3.1-kb fragment. The gene is split into 5 exons. The 5'' untranslated region, the leader peptide and the first 2 NH2-terminal amino acids are fused into the 1st exon. Exons 2 and 3 represent 2 extracellular coding domains of mature p34. The transmembrane domain, cytoplasmic domain and part of the 3'' untranslated region are merged into a 4th exon. The rest of the 3'' untranslated region is in exon 5. The predicted amino acid sequence of mature p34, as deduced from its gene structure, has 229 residues and reveals a single potential disulfide loop (between Cys residues 107 and 163) as well as a 22-amino acid residue membrane integrated segment (residues 193-214). Amino acids (15) (residues 215-229) reside on the cytoplasmic side of the plasma membrane. There is considerable amino acid sequence homology between the 2nd external domains of p34 and p29, as well as the Ig-like 3rd domain of HLA-B7, and .beta.2-microglobulin and the homologous constant region domains of the L and H chains of Ig.