Complete amino acid sequence of an HLA-DR antigen-like beta chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A, -B, and -C antigens.

Abstract

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...

The genetic predisposition to fibrocalculous pancreatic diabetes

“…DQc~ is a Pst 1 2.0 kb genomic fragment and also identifies with the DXc~ gene [19]. DQ[~ is a Ava I cDNA fragment of pDR[31, 0.6 kb in length [20]. Patient DNA was digested with Bgl II (DRc 0 and Taq 1 (DQa/DQ[3).…”

Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (antineutrophil cytoplasmic antibodies) markers.

“…The DRbeta probe was prepared by digestion of DR-beta cDNA clone ( 15 ) with PstI, generating a 520-bp fragment. The DQ-beta probe was prepared by digestion of a DQ-beta cDNA clone (pII-beta-l) (16) with AvaI, generating a 630-bp fragment. The membranes were hybridized at 65°C for 12 h, and subsequently washed as follows: 2x SSC-0.1 % SDS at 65°C for 5 min twice, followed by 0.2x SSC-0.…”

HLA II: The emergence of the molecular model for the human major histocompatibility complex

“…The fact that the allotypic variation in the class I and I1 genes has been found in the alpha-1 and alpha-2 regions of the HLA-A, -B, and -C molecules and the alpha-1 and beta-1 domains of the class I1 genes implies that the domains near the cell membrane have been conserved during evolution, which has been shown to be the case (Auffray et al, 1982;Larhammar et al, 1982;Korman et al, 1982). The alpha-3 domain of class I genes and the alpha-2 and beta-2 domains of the class I1 show significant homology with one another and with the constant regions of human IgG heavy and light chains and with beta-2-microglobulin.…”