Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy
Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 a...
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| Veröffentlicht in: | The Journal of experimental medicine 1996-03, Vol.183 (3), p.829-836 |
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| container_title | The Journal of experimental medicine |
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| creator | Zerva, L Cizman, B Mehra, N K Alahari, S K Murali, R Zmijewski, C M Kamoun, M Monos, D S |
| description | Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule. |
| doi_str_mv | 10.1084/jem.183.3.829 |
| format | Article |
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Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.183.3.829</identifier><identifier>PMID: 8642287</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Alleles ; Amino Acid Sequence ; Arginine ; Chi-Square Distribution ; Crystallography, X-Ray ; Genes, MHC Class II ; Genetic Predisposition to Disease ; Histocompatibility Testing ; HLA-DR Antigens - chemistry ; HLA-DR Antigens - genetics ; HLA-DRB1 Chains ; Humans ; Leprosy, Tuberculoid - epidemiology ; Leprosy, Tuberculoid - genetics ; Leprosy, Tuberculoid - immunology ; Macromolecular Substances ; Models, Molecular ; Molecular Sequence Data ; Mycobacterium leprae ; Polymerase Chain Reaction ; Protein Conformation ; Reference Values ; Risk Factors</subject><ispartof>The Journal of experimental medicine, 1996-03, Vol.183 (3), p.829-836</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-7ce6ad0e503a9d8dc875cf0457de716f27ac0e74e8c97480aee8d9930d0f331f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8642287$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zerva, L</creatorcontrib><creatorcontrib>Cizman, B</creatorcontrib><creatorcontrib>Mehra, N K</creatorcontrib><creatorcontrib>Alahari, S K</creatorcontrib><creatorcontrib>Murali, R</creatorcontrib><creatorcontrib>Zmijewski, C M</creatorcontrib><creatorcontrib>Kamoun, M</creatorcontrib><creatorcontrib>Monos, D S</creatorcontrib><title>Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule.</description><subject>Alleles</subject><subject>Amino Acid Sequence</subject><subject>Arginine</subject><subject>Chi-Square Distribution</subject><subject>Crystallography, X-Ray</subject><subject>Genes, MHC Class II</subject><subject>Genetic Predisposition to Disease</subject><subject>Histocompatibility Testing</subject><subject>HLA-DR Antigens - chemistry</subject><subject>HLA-DR Antigens - genetics</subject><subject>HLA-DRB1 Chains</subject><subject>Humans</subject><subject>Leprosy, Tuberculoid - epidemiology</subject><subject>Leprosy, Tuberculoid - genetics</subject><subject>Leprosy, Tuberculoid - immunology</subject><subject>Macromolecular Substances</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mycobacterium leprae</subject><subject>Polymerase Chain Reaction</subject><subject>Protein Conformation</subject><subject>Reference Values</subject><subject>Risk Factors</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkT1vFDEQhi0ECpdASYnkim6P8dfa2yAdISFIJ0WKoLZ83tnEwbdebC_o-PVZlFMEFdUU76NXM_MQ8obBmoGR7-9xv2ZGrMXa8O4ZWTEloemUMM_JCoDzhgHol-S0lHsAJqVqT8iJaSXnRq_I702-DWMYkbpKp1RCDWkslAmaMtXQaEbDuAT-O1YqaRro1XbTfLr5yKiLESMWGgp1pSQfXMWe_gr1jpa5eJxq2IUY6oHWROu8w-znmEJPI045lcMr8mJwseDr4zwj3y4vvp5fNdvrz1_ON9vGSyZqoz22rgdUIFzXm94brfwAUukeNWsHrp0H1BKN77Q04BBN33UCehiEYIM4Ix8ee6d5t8fe41izi3bKYe_ywSYX7L_JGO7sbfppOeu4UGIpeHcsyOnHjKXafVjui9GNmOZitQHFBYP_gky10DHDF7B5BP3yiJJxeNqGgf1j1S5W7WLVCrtYXfi3f5_wRB81igfTop7Z</recordid><startdate>19960301</startdate><enddate>19960301</enddate><creator>Zerva, L</creator><creator>Cizman, B</creator><creator>Mehra, N K</creator><creator>Alahari, S K</creator><creator>Murali, R</creator><creator>Zmijewski, C M</creator><creator>Kamoun, M</creator><creator>Monos, D S</creator><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19960301</creationdate><title>Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy</title><author>Zerva, L ; Cizman, B ; Mehra, N K ; Alahari, S K ; Murali, R ; Zmijewski, C M ; Kamoun, M ; Monos, D S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-7ce6ad0e503a9d8dc875cf0457de716f27ac0e74e8c97480aee8d9930d0f331f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Alleles</topic><topic>Amino Acid Sequence</topic><topic>Arginine</topic><topic>Chi-Square Distribution</topic><topic>Crystallography, X-Ray</topic><topic>Genes, MHC Class II</topic><topic>Genetic Predisposition to Disease</topic><topic>Histocompatibility Testing</topic><topic>HLA-DR Antigens - chemistry</topic><topic>HLA-DR Antigens - genetics</topic><topic>HLA-DRB1 Chains</topic><topic>Humans</topic><topic>Leprosy, Tuberculoid - epidemiology</topic><topic>Leprosy, Tuberculoid - genetics</topic><topic>Leprosy, Tuberculoid - immunology</topic><topic>Macromolecular Substances</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mycobacterium leprae</topic><topic>Polymerase Chain Reaction</topic><topic>Protein Conformation</topic><topic>Reference Values</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zerva, L</creatorcontrib><creatorcontrib>Cizman, B</creatorcontrib><creatorcontrib>Mehra, N K</creatorcontrib><creatorcontrib>Alahari, S K</creatorcontrib><creatorcontrib>Murali, R</creatorcontrib><creatorcontrib>Zmijewski, C M</creatorcontrib><creatorcontrib>Kamoun, M</creatorcontrib><creatorcontrib>Monos, D S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zerva, L</au><au>Cizman, B</au><au>Mehra, N K</au><au>Alahari, S K</au><au>Murali, R</au><au>Zmijewski, C M</au><au>Kamoun, M</au><au>Monos, D S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>1996-03-01</date><risdate>1996</risdate><volume>183</volume><issue>3</issue><spage>829</spage><epage>836</epage><pages>829-836</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>8642287</pmid><doi>10.1084/jem.183.3.829</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Alleles Amino Acid Sequence Arginine Chi-Square Distribution Crystallography, X-Ray Genes, MHC Class II Genetic Predisposition to Disease Histocompatibility Testing HLA-DR Antigens - chemistry HLA-DR Antigens - genetics HLA-DRB1 Chains Humans Leprosy, Tuberculoid - epidemiology Leprosy, Tuberculoid - genetics Leprosy, Tuberculoid - immunology Macromolecular Substances Models, Molecular Molecular Sequence Data Mycobacterium leprae Polymerase Chain Reaction Protein Conformation Reference Values Risk Factors |
| title | Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy |
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