A Homozygous Cell Line Expresses Multiple HLA - DS Alpha Chains

The human Ia antigens are encoded within the HLA complex on chromosome six and are borne on molecules composed of two noncovalently associated glycoproteins o f 3 4 , 0 0 0 daltons (a chains) and ~28,000 daltons (/3 chains). Ia antigens are important in the effective collaboration between immunocompetent cells in the generation of immune responses; they have also been associated with putative immune response genes and the predisposition to the development of certain diseases. Three types of human Ia molecules have been identified and biochemically characterized: DR, DS (or DC), and SB. DR molecules are defined by their N-terminal amino acid sequence homology to murine I-E molecules (13). HLA-DR homozygous cells appear to express a single DR a chain that associates with either of two distinct DR/3 chains to form two heterodimeric DR molecules (2, 3). SB molecules appear to be structurally different from the corresponding DR molecules, although SB a chains, like DR a chains, are homologous to murine I-E 0~ chains (4). DS (or DC) molecules are defined by their N-terminal amino acid sequence homology to murine I-A molecules (1, 5). Although previous studies indicated that HLA-DR homozygous cells express a single DS molecule, we have recently shown that an HLA-DR5 homozygous cell line expresses at least two distinct DS molecules (6). Therefore, existing evidence at the protein level indicates that HLA-DR homozygous cell lines express at least five Ia molecules: two DR molecules, two DS molecules, and one SB molecule. Serologic testing with anti-Ia allosera has identified two major groups of serologically defined Ia alloantigens: the HLA-DR antigens and the non-DR antigens including the MB (7, 8), MT (9), LB (10), Te (1 1), DC (12, 13), and BR (14-16) alloantigen systems. The serologically defined non-DR Ia alloantigen systems share the common feature that each specificity is found in association with two or more HLA-DR antigens. The determination of the molecular relationships of these serologically defined Ia alloantigens to the biochemically defined Ia molecules (DR, DC, SB) has been the focus of considerable interest. In general, the biochemically defined DR molecules appear to bear the serologThis work was supported by a research grant from the Veterans Administration and by grants from the National Institutes of Health including CA28848 from the National Cancer Institute. R. W. K. is lhe recipient of a New Investigator Research Award (AM32039) from the NIH.