Complete amino acid sequence of pooled papain-solubilized HLA-A, -B, and -C antigens: relatedness to immunoglobulins and internal homologies.

The primary structure of two highly crossreactive human histocompatibility antigens, HLA-A28 and HLA-A2, has been determined to 96% and 90%, respectively, ofthe papainsolubilized molecules. Their sequences have been compared with the sequence of HLA-B7 and with each other in order to outline the sites of diversity. The overall homology between HLA-B7 and these HLA-A antigens is 86%. A large majority of the differences are located between residues 43 and 195. Within this area, substitutions cluster in at least three segments-residues 65-80, 105-116, and 177-194. HLA-A28 and HLA-A2 show 96% homology. Most of the differences fall within segments 65-74 and 107-116. These results strongly support the suggestion that residues in these segments are integral parts of the alloantigenic determinants of HLA-A28 and HLA-A2. It is further proposed that these three clusters may constitute major, albeit not exclusive, sites of antigenic diversity in human histocompatibility antigens. The nature of the differences among HLA-B7, HLA-A28, and HLA-A2. in the first variable segment suggests that gene conversion might play some role in the generation ofHIA polymorphism.

supporting

confidence: 58%

mentioning

confidence: 99%

Structure of crossreactive human histocompatibility antigens HLA-A28 and HLA-A2: possible implications for the generation of HLA polymorphism.

Castro¹,

Strominger²,

Strong³

et al. 1982

“…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).…”

mentioning

confidence: 99%

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.

Larhammar¹,

Schenning²,

Gustafsson³

et al. 1982

Self Cite

290

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...

“…By contrast, f32-microglobulin, which is not encoded in the MHC (4), is essentially invariant within a species. Extensive serological (5,6) and biochemical (7) analyses have been performed in both the human and murine systems, including detailed amino acid sequence determinations (8)(9)(10).…”

mentioning

confidence: 99%

Characterization of a porcine genomic clone encoding a major histocompatibility antigen: expression in mouse L cells.

Singer¹,

Camerini‐Otero²,

Satz³

et al. 1982

A porcine genomic clone encoding a major histocompatibility (MHC) antigen was isolated by direct screening of a swine genomic library with a heterologous human MHC cDNA probe. Mouse L cells transformed with DNA from the clone stably express swine MHC antigen. Pig alloantisera specifically lyse transformant but not control cell lines in a complement-mediated cytotoxicity assay. Direct immunoprecipitation ofradiolabeled cellular protein from transformant lines by pig alloantiserum results in the coprecipitation of swine MHC heavy chain and mouse microglobulin, demonstrating the association ofheterologous subunits of MHC antigens.