The Amino Acid Sequence and Gene Organization of the Heavy Chain of the HLA-DR Antigen: Homology to Immunoglobulins

The amino acid sequence of the heavy chain of HLA-DR antigens has been elucidated from the analysis of a genomic clone coding for this protein. A 3.2-kilobase EcoRI fragment includes four exons containing 227 amino acids out of 229 in the mature HLA-DR heavy chain. One exon (α 2) encodes a domain of 94 amino acids with strong sequence homology both to Ig constant region domains and to Ig-like domains in HLA-B7, β2-microglobulin, and the HLA-DR light chain. These results support a structure for the HLA-DR antigen heterodimer consisting of four extracellular domains, two of which are Ig-like [one in the heavy chain (α 2) and one in the light chain (β 2)]. The third is the amino-terminal polymorphic domain in the light chain (β 1), and the fourth is an invariant domain in the heavy chain (α 1).