Structural and evolutionary analysis of HLA-D-region products.
The major histocompatibility complex (MHC)--HLA in man and H-2 in mouse--encodes two classes of cell-surface antigens involved in the immune response. The amino acid sequences have been determined for a number of these molecules. Class I antigens, typified by the HLA-ABC antigens, are composed of a...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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1984
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| _version_ | 1826256556495208448 |
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| author | Travers, P Blundell, T Sternberg, M Bodmer, W |
| author_facet | Travers, P Blundell, T Sternberg, M Bodmer, W |
| author_sort | Travers, P |
| collection | OXFORD |
| description | The major histocompatibility complex (MHC)--HLA in man and H-2 in mouse--encodes two classes of cell-surface antigens involved in the immune response. The amino acid sequences have been determined for a number of these molecules. Class I antigens, typified by the HLA-ABC antigens, are composed of a 43,000-molecular weight (MW) glycosylated transmembrane polypeptide with three external domains (alpha 1, alpha 2 and alpha 3), of which the one nearest the membrane (alpha 3) is associated with a 12,000-MW nonglycosylated polypeptide, beta 2-microglobulin. The HLA-D-region or class II antigens, DR, DC and SB, are composed of two glycosylated transmembrane polypeptides, of MWs 34,000 (alpha-chain) and 28,000 (beta-chain). Both chains have two external domains which presumably associate with each other, alpha 2, beta 2 being membrane proximal and alpha 1, beta 1 N-terminal and membrane distal. All four membrane-proximal domains (class I alpha 3, beta 2-microglobulin, class II alpha 2 and beta 2) have amino acid sequences that show significant similarities with immunoglobulin constant-region domains. This, together with the similarly placed internal disulphide bonds, suggests they might have an immunoglobulin-like structure (Fig. 1). We have now used computer graphics techniques to predict a detailed three-dimensional structure for the membrane-proximal domains of the class II antigens (alpha 2 and beta 2) based on the known coordinates of immunoglobulin constant domains (Fig. 2). The transmembrane regions of class II antigens have been modelled as two alpha-helices packed together. The proposed structure accounts for conservation of amino acids and leads to evolutionary predictions. |
| first_indexed | 2024-03-06T18:04:06Z |
| format | Journal article |
| id | oxford-uuid:00d41988-5603-4be2-9266-767dc93121e2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:04:06Z |
| publishDate | 1984 |
| record_format | dspace |
| spelling | oxford-uuid:00d41988-5603-4be2-9266-767dc93121e22022-03-26T08:31:41ZStructural and evolutionary analysis of HLA-D-region products.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:00d41988-5603-4be2-9266-767dc93121e2EnglishSymplectic Elements at Oxford1984Travers, PBlundell, TSternberg, MBodmer, WThe major histocompatibility complex (MHC)--HLA in man and H-2 in mouse--encodes two classes of cell-surface antigens involved in the immune response. The amino acid sequences have been determined for a number of these molecules. Class I antigens, typified by the HLA-ABC antigens, are composed of a 43,000-molecular weight (MW) glycosylated transmembrane polypeptide with three external domains (alpha 1, alpha 2 and alpha 3), of which the one nearest the membrane (alpha 3) is associated with a 12,000-MW nonglycosylated polypeptide, beta 2-microglobulin. The HLA-D-region or class II antigens, DR, DC and SB, are composed of two glycosylated transmembrane polypeptides, of MWs 34,000 (alpha-chain) and 28,000 (beta-chain). Both chains have two external domains which presumably associate with each other, alpha 2, beta 2 being membrane proximal and alpha 1, beta 1 N-terminal and membrane distal. All four membrane-proximal domains (class I alpha 3, beta 2-microglobulin, class II alpha 2 and beta 2) have amino acid sequences that show significant similarities with immunoglobulin constant-region domains. This, together with the similarly placed internal disulphide bonds, suggests they might have an immunoglobulin-like structure (Fig. 1). We have now used computer graphics techniques to predict a detailed three-dimensional structure for the membrane-proximal domains of the class II antigens (alpha 2 and beta 2) based on the known coordinates of immunoglobulin constant domains (Fig. 2). The transmembrane regions of class II antigens have been modelled as two alpha-helices packed together. The proposed structure accounts for conservation of amino acids and leads to evolutionary predictions. |
| spellingShingle | Travers, P Blundell, T Sternberg, M Bodmer, W Structural and evolutionary analysis of HLA-D-region products. |
| title | Structural and evolutionary analysis of HLA-D-region products. |
| title_full | Structural and evolutionary analysis of HLA-D-region products. |
| title_fullStr | Structural and evolutionary analysis of HLA-D-region products. |
| title_full_unstemmed | Structural and evolutionary analysis of HLA-D-region products. |
| title_short | Structural and evolutionary analysis of HLA-D-region products. |
| title_sort | structural and evolutionary analysis of hla d region products |
| work_keys_str_mv | AT traversp structuralandevolutionaryanalysisofhladregionproducts AT blundellt structuralandevolutionaryanalysisofhladregionproducts AT sternbergm structuralandevolutionaryanalysisofhladregionproducts AT bodmerw structuralandevolutionaryanalysisofhladregionproducts |