[Primary structure of class II human histocompatibility antigens. 2nd Communication. Amino acid sequence of the N-terminal 179 residues of the alpha-chain of an HLA-Dw2/DR2 alloantigen (author's transl)].

From a lymphoblastoid homozygous cell-line (HLA-A3,3; B7,7; Dw2,2; DR2,2) the alpha-chain of the HLA-Dw2/DR2 antigen was isolated by an exclusively chemical procedure. The alpha- was separated from the beta-chain by chromatography with hydroxylapatite in Na-dodecyl sulfate. Here we describe the amino acid sequence of the alpha-chain up to Position 179. The molecule is divided into two domains which do not appear homologous to each other but show a significant homology to the beta-chain (21.2%). The similarity is larger in the second (27%) than in the first (15.5%) domain, indicating a different evolutionary relationship for both parts. In contrast to the beta-chain both domains contain an N-glycosidically linked carbohydrate. The methionines are positioned only in the N-terminal, the cysteines exclusively in the C-terminal domain. Only the latter can therefore be stabilized by a disulfide bridge. As with the beta-chain the regions around the cysteines show a remarkable similarity with the constant C-terminal domains of k-, lambda-, alpha-, gamma-, sigma-, epsilon- and mu-chains of immunoglobulins. Although to a considerably lesser extent, the alpha-chain preparation also shows a heterogeneity at the protein level. Since the employed cell-line is homozygous with regard to HLA-D/DR, our results indicate that at least two alpha-chain genes exist in the HLA-D/DR-region. Together with the already published sequence of the beta-chain, the extracellular part of an histocompatibility antigen of the HLA-D type is now known.