The complete nucleotide sequence of an HLA-DR antigen-like (3-chain cDNA clone was determined. The 1,080 base pairs include the complete coding region and most of the untranslated portion. The predicted amino acid sequence has 229 residues. The .8 chain contains two immunoglobulin-like disulfide loops and a 21-amino acid residue membrane-integrated segment. Ten amino acid residues reside on the cytoplasmic side of the plasma membrane. The single asparagine-linked carbohydrate moiety is attached to asparagine-19. The NH2-terminal 91 residues of the (3 chain are homologous to the corresponding region of HLA-A, -B, and -C antigen heavy chains. Residues of the ( chain display statistically significant homology to members of the immunoglobulin family, P2-microglobulin, and the immunoglobulin-like domain of HLA-A, -B, and -C antigen heavy chains. These data establish that the major histocompatibility antigens of class I and class II type and the constant regions of immunoglobulins are evolutionarily related.The major histocompatibility complex encompasses genes that control two types of cell surface-expressed transplantation antigens (see ref. 1). The class I antigens, termed HLA-A, -B, and -C antigens in man and H-2 K, D, and L in the mouse, are integral membrane proteins displaying extensive genetic polymorphism (2). They are composed of one invariant chain, /32-microglobulin, and one heavy chain (3,4). The heavy chain spans the lipid bilayer and has three extracellular domains, each having 90 amino acid residues (for review, see ref. 5). The second domain and the domain attached to the membrane-spanning segment contain immunoglobulin-like disulfide loops (6). However, only the latter domain is homologous in primary structure to immunoglobulin constant domains (7)(8)(9)(10)(11). /32-Microglobulin is also evolutionarily related to the immunoglobulin chains (12).The class II molecules, termed HLA-DR and Ia-antigens in man and mouse, respectively, are composed of dissimilar subunits, called a and /3 chains (13), both of which are integral membrane proteins that leave their COOH-terminal regions on the cytoplasmic side of the plasma membrane (14, 15). Class II antigens have been implicated in a variety ofimmunoregulatory events (16)(17)(18). Their role in the presentation of foreign antigens to T-helper cells has received much attention (see ref. 19). In the latter context, it appeared of interest to examine the primary structure of class II molecules to find out whether these molecules, like the class I antigens, display amino acid sequence homology with immunoglobulins.Recently, several groups have succeeded in cloning cDNA corresponding to the heavy chain of class I antigens (20-23), a prerequisite for obtaining primary structure information at a rapid rate. Consequently, we and others have isolated cDNA clones corresponding to the a (24, 25) and ,B chains (26) of HLA-DR-like antigens. In this communication, we provide the complete nucleotide sequence of one of the P-chain cDNA clones and demonstrate that t...

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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We have isolated and sequenced the complete murine I-E alpha immune response gene of the H-2db haplotype. The I-E alpha d gene consists of 5300 basepairs and is organized into five or possibly six exons that correspond to different domains of the alpha chain. The amino acid sequence deduced from the I-E alpha gene shows 75% homology to its human counterpart, the HLA-DR alpha chain. The absence of I-E antigen in H-2 mice is due to lack of E alpha chain synthesis. We show here that this defect is caused by a deletion in the 5' end of the I-E alpha b gene.