At least three class II antigens, all composed of an alpha and a beta subunit, are encoded in the human major histocompatibility complex, i.e., DR, DC and SB. Two cDNA clones, encoding a DC alpha and a DC beta chain, respectively, were isolated from a cDNA library of the lymphoblastoid cell line Raji (DR3,w6). The two polypeptides predicted from the nucleotide sequences of these clones are each composed of a signal peptide, two extracellular domains, a hydrophobic transmembrane region and a short cytoplasmic tail. Comparison of the DC alpha sequence with two previously published partial sequences shows that the majority of the differences is located in the amino‐terminal domain. The differences are not randomly distributed; a cluster of replacements is present in the central portion of the amino‐terminal domain. Likewise, the allelic polymorphism of the DC beta chains occurs preferentially in the amino‐terminal domain, where three minor clusters of replacements can be discerned. The non‐random distribution of the variability of DC alpha and beta chains may be due to phenotypic selection against replacement substitutions in the second domains of the polypeptides.

The HLA-D locus in the major histocompatibility complex controls the expression of the genetically polymorphic HLA-DR antigens. mRNA coding for the A chains of these antigens was partially purified from the human lymphoblastoid cell line Raji. The mRNA was copied into double-stranded cDNA and cloned in Escherichia coli. One clone, pDR-(3-1, obtained by hybrid selection, carries a 1070-base-pair insert comprising all ofthe coding region except the signal sequence and a substantial portion of the untranslated region. To identify pDR-.3-1, highly purified HLA-DR antigen (3 chains derived from Raji cells were subjected to NH2-terminal amino acid sequence determination. This sequence displayed extensive homology with that deduced from the nucleotide sequence at the 5' end of the pDR-P-I coding region. Taken together, the amino acid and nucleotide sequences strongly argue in favor of Raji cells containing at least two (-chain loci.

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