Determinants of T cell reactivity to the Mycobacterium leprae GroES homologue
The 10-kDa protein Ag of Mycobacterium leprae, a human GroES hsp10 cognate, is a major T cell Ag in human leprosy infection. We investigated the mechanism for T cell responsiveness to this Ag according to the trimolecular interaction between T cell, peptide, and Ag-presenting element. This research...
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Veröffentlicht in: | The Journal of immunology (1950) 1997-07, Vol.159 (1), p.335-343 |
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container_title | The Journal of immunology (1950) |
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creator | Kim, J Sette, A Rodda, S Southwood, S Sieling, PA Mehra, V Ohmen, JD Oliveros, J Appella, E Higashimoto, Y Rea, TH Bloom, BR Modlin, RL |
description | The 10-kDa protein Ag of Mycobacterium leprae, a human GroES hsp10 cognate, is a major T cell Ag in human leprosy infection. We investigated the mechanism for T cell responsiveness to this Ag according to the trimolecular interaction between T cell, peptide, and Ag-presenting element. This research was accomplished by mapping T cell epitopes in leprosy patients and correlating these responses with peptide-MHC binding affinities. We found that the majority of tuberculoid leprosy patients responded to peptides corresponding to residues 25-39 and 28-42. Truncation analysis of these peptides mapped the exact epitope to be within the overlapping region comprising residues 28-39. Responsiveness was correlated with the HLA-DRB5*0101 allele, which bound the peptides with moderate affinity. This allele is linked to HLA-DR2, which is associated with the resistant form of leprosy. Therefore, T cell responsiveness in tuberculoid leprosy may be mediated by the ability of HLA-DRB5*0101 to bind and present peptides of the immunodominant 10-kDa Ag. |
doi_str_mv | 10.4049/jimmunol.159.1.335 |
format | Article |
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We investigated the mechanism for T cell responsiveness to this Ag according to the trimolecular interaction between T cell, peptide, and Ag-presenting element. This research was accomplished by mapping T cell epitopes in leprosy patients and correlating these responses with peptide-MHC binding affinities. We found that the majority of tuberculoid leprosy patients responded to peptides corresponding to residues 25-39 and 28-42. Truncation analysis of these peptides mapped the exact epitope to be within the overlapping region comprising residues 28-39. Responsiveness was correlated with the HLA-DRB5*0101 allele, which bound the peptides with moderate affinity. This allele is linked to HLA-DR2, which is associated with the resistant form of leprosy. Therefore, T cell responsiveness in tuberculoid leprosy may be mediated by the ability of HLA-DRB5*0101 to bind and present peptides of the immunodominant 10-kDa Ag.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.159.1.335</identifier><identifier>PMID: 9200471</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Alleles ; Amino Acid Sequence ; Antigens, Bacterial - immunology ; Chaperonin 10 - genetics ; Chaperonin 10 - immunology ; Clone Cells ; Epitopes, T-Lymphocyte - immunology ; HLA-DR Antigens - genetics ; HLA-DR Antigens - immunology ; HLA-DRB5 Chains ; Humans ; Molecular Sequence Data ; Mycobacterium leprae ; Mycobacterium leprae - immunology ; Sequence Homology, Amino Acid ; T-Lymphocytes - immunology</subject><ispartof>The Journal of immunology (1950), 1997-07, Vol.159 (1), p.335-343</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c336t-2ed4cbd2ca22a1f5fcfecd2447e0a5c994c2a282b5c3881df1cf116d5c0aad373</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9200471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, J</creatorcontrib><creatorcontrib>Sette, A</creatorcontrib><creatorcontrib>Rodda, S</creatorcontrib><creatorcontrib>Southwood, S</creatorcontrib><creatorcontrib>Sieling, PA</creatorcontrib><creatorcontrib>Mehra, V</creatorcontrib><creatorcontrib>Ohmen, JD</creatorcontrib><creatorcontrib>Oliveros, J</creatorcontrib><creatorcontrib>Appella, E</creatorcontrib><creatorcontrib>Higashimoto, Y</creatorcontrib><creatorcontrib>Rea, TH</creatorcontrib><creatorcontrib>Bloom, BR</creatorcontrib><creatorcontrib>Modlin, RL</creatorcontrib><title>Determinants of T cell reactivity to the Mycobacterium leprae GroES homologue</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>The 10-kDa protein Ag of Mycobacterium leprae, a human GroES hsp10 cognate, is a major T cell Ag in human leprosy infection. We investigated the mechanism for T cell responsiveness to this Ag according to the trimolecular interaction between T cell, peptide, and Ag-presenting element. This research was accomplished by mapping T cell epitopes in leprosy patients and correlating these responses with peptide-MHC binding affinities. We found that the majority of tuberculoid leprosy patients responded to peptides corresponding to residues 25-39 and 28-42. Truncation analysis of these peptides mapped the exact epitope to be within the overlapping region comprising residues 28-39. Responsiveness was correlated with the HLA-DRB5*0101 allele, which bound the peptides with moderate affinity. This allele is linked to HLA-DR2, which is associated with the resistant form of leprosy. Therefore, T cell responsiveness in tuberculoid leprosy may be mediated by the ability of HLA-DRB5*0101 to bind and present peptides of the immunodominant 10-kDa Ag.</description><subject>Alleles</subject><subject>Amino Acid Sequence</subject><subject>Antigens, Bacterial - immunology</subject><subject>Chaperonin 10 - genetics</subject><subject>Chaperonin 10 - immunology</subject><subject>Clone Cells</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>HLA-DR Antigens - genetics</subject><subject>HLA-DR Antigens - immunology</subject><subject>HLA-DRB5 Chains</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>Mycobacterium leprae</subject><subject>Mycobacterium leprae - immunology</subject><subject>Sequence Homology, Amino Acid</subject><subject>T-Lymphocytes - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1PwzAMhiMEGmPwB5CQcuLWkqRNP45ojIG0iQPjHKWpu2ZqlpG0VPv3dNqAIydL1uPX9oPQLSVhTOL8YaON6ba2CSnPQxpGET9DY8o5CZKEJOdoTAhjAU2T9BJdeb8hhCSExSM0yhkhcUrHaPkELTijt3LbemwrvMIKmgY7kKrVX7rd49bitga83CtbDE1wujO4gZ2TgOfOzt5xbY1t7LqDa3RRycbDzalO0MfzbDV9CRZv89fp4yJQUZS0AYMyVkXJlGRM0opXqgJVsjhOgUiu8jxWTLKMFVxFWUbLiqqK0qTkikhZRmk0QffH3J2znx34VhjtD3fLLdjOizQnaTp8-C9IBx8Zz_kAsiOonPXeQSV2Thvp9oIScZAtfmSLQbagYpA9DN2d0rvCQPk7crL7t73W67rXDoQ3smkGmoq-7_-CvgGjYotY</recordid><startdate>19970701</startdate><enddate>19970701</enddate><creator>Kim, J</creator><creator>Sette, A</creator><creator>Rodda, S</creator><creator>Southwood, S</creator><creator>Sieling, PA</creator><creator>Mehra, V</creator><creator>Ohmen, JD</creator><creator>Oliveros, J</creator><creator>Appella, E</creator><creator>Higashimoto, Y</creator><creator>Rea, TH</creator><creator>Bloom, BR</creator><creator>Modlin, RL</creator><general>Am Assoc Immnol</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></search><sort><creationdate>19970701</creationdate><title>Determinants of T cell reactivity to the Mycobacterium leprae GroES homologue</title><author>Kim, J ; Sette, A ; Rodda, S ; Southwood, S ; Sieling, PA ; Mehra, V ; Ohmen, JD ; Oliveros, J ; Appella, E ; Higashimoto, Y ; Rea, TH ; Bloom, BR ; Modlin, RL</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c336t-2ed4cbd2ca22a1f5fcfecd2447e0a5c994c2a282b5c3881df1cf116d5c0aad373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Alleles</topic><topic>Amino Acid Sequence</topic><topic>Antigens, Bacterial - immunology</topic><topic>Chaperonin 10 - genetics</topic><topic>Chaperonin 10 - immunology</topic><topic>Clone Cells</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>HLA-DR Antigens - genetics</topic><topic>HLA-DR Antigens - immunology</topic><topic>HLA-DRB5 Chains</topic><topic>Humans</topic><topic>Molecular Sequence Data</topic><topic>Mycobacterium leprae</topic><topic>Mycobacterium leprae - immunology</topic><topic>Sequence Homology, Amino Acid</topic><topic>T-Lymphocytes - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, J</creatorcontrib><creatorcontrib>Sette, A</creatorcontrib><creatorcontrib>Rodda, S</creatorcontrib><creatorcontrib>Southwood, S</creatorcontrib><creatorcontrib>Sieling, PA</creatorcontrib><creatorcontrib>Mehra, V</creatorcontrib><creatorcontrib>Ohmen, JD</creatorcontrib><creatorcontrib>Oliveros, J</creatorcontrib><creatorcontrib>Appella, E</creatorcontrib><creatorcontrib>Higashimoto, Y</creatorcontrib><creatorcontrib>Rea, TH</creatorcontrib><creatorcontrib>Bloom, BR</creatorcontrib><creatorcontrib>Modlin, RL</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><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, J</au><au>Sette, A</au><au>Rodda, S</au><au>Southwood, S</au><au>Sieling, PA</au><au>Mehra, V</au><au>Ohmen, JD</au><au>Oliveros, J</au><au>Appella, E</au><au>Higashimoto, Y</au><au>Rea, TH</au><au>Bloom, BR</au><au>Modlin, RL</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Determinants of T cell reactivity to the Mycobacterium leprae GroES homologue</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>1997-07-01</date><risdate>1997</risdate><volume>159</volume><issue>1</issue><spage>335</spage><epage>343</epage><pages>335-343</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>The 10-kDa protein Ag of Mycobacterium leprae, a human GroES hsp10 cognate, is a major T cell Ag in human leprosy infection. We investigated the mechanism for T cell responsiveness to this Ag according to the trimolecular interaction between T cell, peptide, and Ag-presenting element. This research was accomplished by mapping T cell epitopes in leprosy patients and correlating these responses with peptide-MHC binding affinities. We found that the majority of tuberculoid leprosy patients responded to peptides corresponding to residues 25-39 and 28-42. Truncation analysis of these peptides mapped the exact epitope to be within the overlapping region comprising residues 28-39. Responsiveness was correlated with the HLA-DRB5*0101 allele, which bound the peptides with moderate affinity. This allele is linked to HLA-DR2, which is associated with the resistant form of leprosy. Therefore, T cell responsiveness in tuberculoid leprosy may be mediated by the ability of HLA-DRB5*0101 to bind and present peptides of the immunodominant 10-kDa Ag.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>9200471</pmid><doi>10.4049/jimmunol.159.1.335</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Alleles Amino Acid Sequence Antigens, Bacterial - immunology Chaperonin 10 - genetics Chaperonin 10 - immunology Clone Cells Epitopes, T-Lymphocyte - immunology HLA-DR Antigens - genetics HLA-DR Antigens - immunology HLA-DRB5 Chains Humans Molecular Sequence Data Mycobacterium leprae Mycobacterium leprae - immunology Sequence Homology, Amino Acid T-Lymphocytes - immunology |
title | Determinants of T cell reactivity to the Mycobacterium leprae GroES homologue |
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