A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax 301-309 -Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients
We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax -specific CD8 cytotoxic T cells (Tax -CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02 )...
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| creator | Ishihara, Yuko Tanaka, Yukie Kobayashi, Seiichiro Kawamura, Koji Nakasone, Hideki Gomyo, Ayumi Hayakawa, Jin Tamaki, Masaharu Akahoshi, Yu Harada, Naonori Kusuda, Machiko Kameda, Kazuaki Ugai, Tomotaka Wada, Hidenori Sakamoto, Kana Sato, Miki Terasako-Saito, Kiriko Kikuchi, Misato Kimura, Shun-Ichi Tanihara, Aki Kako, Shinichi Uchimaru, Kaoru Kanda, Yoshinobu |
| description | We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax
-specific CD8
cytotoxic T cells (Tax
-CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02
) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR
CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax
-CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax
-CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax
-CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax
-CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax
-CTLs, 1,458 Tax
-CTLs and 140 clones were identified in this cohort. Tax
-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR
CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02
HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR
CTL response in the progression from carrier state to ATL.
ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the proliferation of HTLV-1-infected lymphocytes and is also a major target antigen for CD8
CTLs. In our previous evaluation of Tax
-CTLs, we found that a unique amino acid sequence motif, PDR, in CDR3 of the TCR-β chain of Tax
-CTLs was conserved among ATL patients after allo-HSCT. Furthermore, the PDR
Tax
-CTL clones selectively expanded and showed strong cytotoxic activities against HTLV-1. On the other hand, it remains unclear how Tax
-CTL repertoire exists in ACs. In this study, we comprehensively compared Tax-specific TCR repertoires at the single-cell level between ACs and ATL patients. Tax
-CTLs sho |
| doi_str_mv | 10.1128/JVI.00974-17 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1128_JVI_00974_17</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>28724766</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1417-6ec496e75cb90038fe2e9946df804eacbb332c774975ab52586fabeb0e9761c83</originalsourceid><addsrcrecordid>eNo9kU1v1DAQhi0EokvLjTOaH4Bb23HimFu0KmzRSq1oWvUWOc5EGPKF7aDm3_JTyLJtTzOH531npIeQD5ydcy7yi2_3V-eMaSUpV6_IhjOd0zTl8jXZMCYETZP84YS8C-EnY1zKTL4lJyJXQqos25C_BdwN7veMUNItdh18R4tTHD0UvRtGKKxr4BZXYLC4Lh3aiA3UC-zm3gzPqf3STz_G6MfJWbh3fg5QLhMCh9I8QsI4TZgGejuhde2KbJc4xvFx3Uo4FARwA-z2BS2E_MwEvRmDi-4PQhHW5jj2Jh5SxnuHPoAZGiiauYsv93H-hb0zF8dHegM3awKHGM7Im9Z0Ad8_zVNy9-Wy3O7o_vrr1bbYU8slVzRDK3WGKrW1ZizJWxSotcyaNmcSja3rJBFWKalVaupUpHnWmhprhlpl3ObJKfl07LV-DMFjW03e9cYvFWfVQVS1iqr-i6q4WvGPR3ya6x6bF_jZTPIPUt6ORw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax 301-309 -Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Ishihara, Yuko ; Tanaka, Yukie ; Kobayashi, Seiichiro ; Kawamura, Koji ; Nakasone, Hideki ; Gomyo, Ayumi ; Hayakawa, Jin ; Tamaki, Masaharu ; Akahoshi, Yu ; Harada, Naonori ; Kusuda, Machiko ; Kameda, Kazuaki ; Ugai, Tomotaka ; Wada, Hidenori ; Sakamoto, Kana ; Sato, Miki ; Terasako-Saito, Kiriko ; Kikuchi, Misato ; Kimura, Shun-Ichi ; Tanihara, Aki ; Kako, Shinichi ; Uchimaru, Kaoru ; Kanda, Yoshinobu</creator><contributor>Kirchhoff, Frank</contributor><creatorcontrib>Ishihara, Yuko ; Tanaka, Yukie ; Kobayashi, Seiichiro ; Kawamura, Koji ; Nakasone, Hideki ; Gomyo, Ayumi ; Hayakawa, Jin ; Tamaki, Masaharu ; Akahoshi, Yu ; Harada, Naonori ; Kusuda, Machiko ; Kameda, Kazuaki ; Ugai, Tomotaka ; Wada, Hidenori ; Sakamoto, Kana ; Sato, Miki ; Terasako-Saito, Kiriko ; Kikuchi, Misato ; Kimura, Shun-Ichi ; Tanihara, Aki ; Kako, Shinichi ; Uchimaru, Kaoru ; Kanda, Yoshinobu ; Kirchhoff, Frank</creatorcontrib><description>We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax
-specific CD8
cytotoxic T cells (Tax
-CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02
) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR
CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax
-CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax
-CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax
-CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax
-CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax
-CTLs, 1,458 Tax
-CTLs and 140 clones were identified in this cohort. Tax
-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR
CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02
HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR
CTL response in the progression from carrier state to ATL.
ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the proliferation of HTLV-1-infected lymphocytes and is also a major target antigen for CD8
CTLs. In our previous evaluation of Tax
-CTLs, we found that a unique amino acid sequence motif, PDR, in CDR3 of the TCR-β chain of Tax
-CTLs was conserved among ATL patients after allo-HSCT. Furthermore, the PDR
Tax
-CTL clones selectively expanded and showed strong cytotoxic activities against HTLV-1. On the other hand, it remains unclear how Tax
-CTL repertoire exists in ACs. In this study, we comprehensively compared Tax-specific TCR repertoires at the single-cell level between ACs and ATL patients. Tax
-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was conserved in all ACs and ATL patients, regardless of clinical subtype in HTLV-1 infection.</description><identifier>ISSN: 0022-538X</identifier><identifier>EISSN: 1098-5514</identifier><identifier>DOI: 10.1128/JVI.00974-17</identifier><identifier>PMID: 28724766</identifier><language>eng</language><publisher>United States</publisher><subject>Amino Acid Sequence - genetics ; Antigens, CD7 - metabolism ; Cell Adhesion Molecule-1 ; Cell Adhesion Molecules - metabolism ; Cells, Cultured ; Gene Products, tax - genetics ; Gene Products, tax - immunology ; HLA-A24 Antigen - genetics ; HLA-A24 Antigen - immunology ; HTLV-I Infections - pathology ; HTLV-I Infections - virology ; Human T-lymphotropic virus 1 - genetics ; Human T-lymphotropic virus 1 - immunology ; Humans ; Immunoglobulins - metabolism ; Immunologic Memory - immunology ; Leukemia-Lymphoma, Adult T-Cell - genetics ; Leukemia-Lymphoma, Adult T-Cell - immunology ; Receptors, Antigen, T-Cell - genetics ; Receptors, Antigen, T-Cell - immunology ; T-Lymphocytes, Cytotoxic - immunology</subject><ispartof>Journal of virology, 2017-10, Vol.91 (19)</ispartof><rights>Copyright © 2017 American Society for Microbiology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1417-6ec496e75cb90038fe2e9946df804eacbb332c774975ab52586fabeb0e9761c83</citedby><cites>FETCH-LOGICAL-c1417-6ec496e75cb90038fe2e9946df804eacbb332c774975ab52586fabeb0e9761c83</cites></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/28724766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kirchhoff, Frank</contributor><creatorcontrib>Ishihara, Yuko</creatorcontrib><creatorcontrib>Tanaka, Yukie</creatorcontrib><creatorcontrib>Kobayashi, Seiichiro</creatorcontrib><creatorcontrib>Kawamura, Koji</creatorcontrib><creatorcontrib>Nakasone, Hideki</creatorcontrib><creatorcontrib>Gomyo, Ayumi</creatorcontrib><creatorcontrib>Hayakawa, Jin</creatorcontrib><creatorcontrib>Tamaki, Masaharu</creatorcontrib><creatorcontrib>Akahoshi, Yu</creatorcontrib><creatorcontrib>Harada, Naonori</creatorcontrib><creatorcontrib>Kusuda, Machiko</creatorcontrib><creatorcontrib>Kameda, Kazuaki</creatorcontrib><creatorcontrib>Ugai, Tomotaka</creatorcontrib><creatorcontrib>Wada, Hidenori</creatorcontrib><creatorcontrib>Sakamoto, Kana</creatorcontrib><creatorcontrib>Sato, Miki</creatorcontrib><creatorcontrib>Terasako-Saito, Kiriko</creatorcontrib><creatorcontrib>Kikuchi, Misato</creatorcontrib><creatorcontrib>Kimura, Shun-Ichi</creatorcontrib><creatorcontrib>Tanihara, Aki</creatorcontrib><creatorcontrib>Kako, Shinichi</creatorcontrib><creatorcontrib>Uchimaru, Kaoru</creatorcontrib><creatorcontrib>Kanda, Yoshinobu</creatorcontrib><title>A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax 301-309 -Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients</title><title>Journal of virology</title><addtitle>J Virol</addtitle><description>We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax
-specific CD8
cytotoxic T cells (Tax
-CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02
) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR
CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax
-CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax
-CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax
-CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax
-CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax
-CTLs, 1,458 Tax
-CTLs and 140 clones were identified in this cohort. Tax
-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR
CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02
HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR
CTL response in the progression from carrier state to ATL.
ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the proliferation of HTLV-1-infected lymphocytes and is also a major target antigen for CD8
CTLs. In our previous evaluation of Tax
-CTLs, we found that a unique amino acid sequence motif, PDR, in CDR3 of the TCR-β chain of Tax
-CTLs was conserved among ATL patients after allo-HSCT. Furthermore, the PDR
Tax
-CTL clones selectively expanded and showed strong cytotoxic activities against HTLV-1. On the other hand, it remains unclear how Tax
-CTL repertoire exists in ACs. In this study, we comprehensively compared Tax-specific TCR repertoires at the single-cell level between ACs and ATL patients. Tax
-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was conserved in all ACs and ATL patients, regardless of clinical subtype in HTLV-1 infection.</description><subject>Amino Acid Sequence - genetics</subject><subject>Antigens, CD7 - metabolism</subject><subject>Cell Adhesion Molecule-1</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cells, Cultured</subject><subject>Gene Products, tax - genetics</subject><subject>Gene Products, tax - immunology</subject><subject>HLA-A24 Antigen - genetics</subject><subject>HLA-A24 Antigen - immunology</subject><subject>HTLV-I Infections - pathology</subject><subject>HTLV-I Infections - virology</subject><subject>Human T-lymphotropic virus 1 - genetics</subject><subject>Human T-lymphotropic virus 1 - immunology</subject><subject>Humans</subject><subject>Immunoglobulins - metabolism</subject><subject>Immunologic Memory - immunology</subject><subject>Leukemia-Lymphoma, Adult T-Cell - genetics</subject><subject>Leukemia-Lymphoma, Adult T-Cell - immunology</subject><subject>Receptors, Antigen, T-Cell - genetics</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><issn>0022-538X</issn><issn>1098-5514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kU1v1DAQhi0EokvLjTOaH4Bb23HimFu0KmzRSq1oWvUWOc5EGPKF7aDm3_JTyLJtTzOH531npIeQD5ydcy7yi2_3V-eMaSUpV6_IhjOd0zTl8jXZMCYETZP84YS8C-EnY1zKTL4lJyJXQqos25C_BdwN7veMUNItdh18R4tTHD0UvRtGKKxr4BZXYLC4Lh3aiA3UC-zm3gzPqf3STz_G6MfJWbh3fg5QLhMCh9I8QsI4TZgGejuhde2KbJc4xvFx3Uo4FARwA-z2BS2E_MwEvRmDi-4PQhHW5jj2Jh5SxnuHPoAZGiiauYsv93H-hb0zF8dHegM3awKHGM7Im9Z0Ad8_zVNy9-Wy3O7o_vrr1bbYU8slVzRDK3WGKrW1ZizJWxSotcyaNmcSja3rJBFWKalVaupUpHnWmhprhlpl3ObJKfl07LV-DMFjW03e9cYvFWfVQVS1iqr-i6q4WvGPR3ya6x6bF_jZTPIPUt6ORw</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Ishihara, Yuko</creator><creator>Tanaka, Yukie</creator><creator>Kobayashi, Seiichiro</creator><creator>Kawamura, Koji</creator><creator>Nakasone, Hideki</creator><creator>Gomyo, Ayumi</creator><creator>Hayakawa, Jin</creator><creator>Tamaki, Masaharu</creator><creator>Akahoshi, Yu</creator><creator>Harada, Naonori</creator><creator>Kusuda, Machiko</creator><creator>Kameda, Kazuaki</creator><creator>Ugai, Tomotaka</creator><creator>Wada, Hidenori</creator><creator>Sakamoto, Kana</creator><creator>Sato, Miki</creator><creator>Terasako-Saito, Kiriko</creator><creator>Kikuchi, Misato</creator><creator>Kimura, Shun-Ichi</creator><creator>Tanihara, Aki</creator><creator>Kako, Shinichi</creator><creator>Uchimaru, Kaoru</creator><creator>Kanda, Yoshinobu</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20171001</creationdate><title>A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax 301-309 -Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients</title><author>Ishihara, Yuko ; Tanaka, Yukie ; Kobayashi, Seiichiro ; Kawamura, Koji ; Nakasone, Hideki ; Gomyo, Ayumi ; Hayakawa, Jin ; Tamaki, Masaharu ; Akahoshi, Yu ; Harada, Naonori ; Kusuda, Machiko ; Kameda, Kazuaki ; Ugai, Tomotaka ; Wada, Hidenori ; Sakamoto, Kana ; Sato, Miki ; Terasako-Saito, Kiriko ; Kikuchi, Misato ; Kimura, Shun-Ichi ; Tanihara, Aki ; Kako, Shinichi ; Uchimaru, Kaoru ; Kanda, Yoshinobu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1417-6ec496e75cb90038fe2e9946df804eacbb332c774975ab52586fabeb0e9761c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Amino Acid Sequence - genetics</topic><topic>Antigens, CD7 - metabolism</topic><topic>Cell Adhesion Molecule-1</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cells, Cultured</topic><topic>Gene Products, tax - genetics</topic><topic>Gene Products, tax - immunology</topic><topic>HLA-A24 Antigen - genetics</topic><topic>HLA-A24 Antigen - immunology</topic><topic>HTLV-I Infections - pathology</topic><topic>HTLV-I Infections - virology</topic><topic>Human T-lymphotropic virus 1 - genetics</topic><topic>Human T-lymphotropic virus 1 - immunology</topic><topic>Humans</topic><topic>Immunoglobulins - metabolism</topic><topic>Immunologic Memory - immunology</topic><topic>Leukemia-Lymphoma, Adult T-Cell - genetics</topic><topic>Leukemia-Lymphoma, Adult T-Cell - immunology</topic><topic>Receptors, Antigen, T-Cell - genetics</topic><topic>Receptors, Antigen, T-Cell - immunology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ishihara, Yuko</creatorcontrib><creatorcontrib>Tanaka, Yukie</creatorcontrib><creatorcontrib>Kobayashi, Seiichiro</creatorcontrib><creatorcontrib>Kawamura, Koji</creatorcontrib><creatorcontrib>Nakasone, Hideki</creatorcontrib><creatorcontrib>Gomyo, Ayumi</creatorcontrib><creatorcontrib>Hayakawa, Jin</creatorcontrib><creatorcontrib>Tamaki, Masaharu</creatorcontrib><creatorcontrib>Akahoshi, Yu</creatorcontrib><creatorcontrib>Harada, Naonori</creatorcontrib><creatorcontrib>Kusuda, Machiko</creatorcontrib><creatorcontrib>Kameda, Kazuaki</creatorcontrib><creatorcontrib>Ugai, Tomotaka</creatorcontrib><creatorcontrib>Wada, Hidenori</creatorcontrib><creatorcontrib>Sakamoto, Kana</creatorcontrib><creatorcontrib>Sato, Miki</creatorcontrib><creatorcontrib>Terasako-Saito, Kiriko</creatorcontrib><creatorcontrib>Kikuchi, Misato</creatorcontrib><creatorcontrib>Kimura, Shun-Ichi</creatorcontrib><creatorcontrib>Tanihara, Aki</creatorcontrib><creatorcontrib>Kako, Shinichi</creatorcontrib><creatorcontrib>Uchimaru, Kaoru</creatorcontrib><creatorcontrib>Kanda, Yoshinobu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ishihara, Yuko</au><au>Tanaka, Yukie</au><au>Kobayashi, Seiichiro</au><au>Kawamura, Koji</au><au>Nakasone, Hideki</au><au>Gomyo, Ayumi</au><au>Hayakawa, Jin</au><au>Tamaki, Masaharu</au><au>Akahoshi, Yu</au><au>Harada, Naonori</au><au>Kusuda, Machiko</au><au>Kameda, Kazuaki</au><au>Ugai, Tomotaka</au><au>Wada, Hidenori</au><au>Sakamoto, Kana</au><au>Sato, Miki</au><au>Terasako-Saito, Kiriko</au><au>Kikuchi, Misato</au><au>Kimura, Shun-Ichi</au><au>Tanihara, Aki</au><au>Kako, Shinichi</au><au>Uchimaru, Kaoru</au><au>Kanda, Yoshinobu</au><au>Kirchhoff, Frank</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax 301-309 -Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients</atitle><jtitle>Journal of virology</jtitle><addtitle>J Virol</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>91</volume><issue>19</issue><issn>0022-538X</issn><eissn>1098-5514</eissn><abstract>We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax
-specific CD8
cytotoxic T cells (Tax
-CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02
) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR
CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax
-CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax
-CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax
-CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax
-CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax
-CTLs, 1,458 Tax
-CTLs and 140 clones were identified in this cohort. Tax
-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR
CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02
HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR
CTL response in the progression from carrier state to ATL.
ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the proliferation of HTLV-1-infected lymphocytes and is also a major target antigen for CD8
CTLs. In our previous evaluation of Tax
-CTLs, we found that a unique amino acid sequence motif, PDR, in CDR3 of the TCR-β chain of Tax
-CTLs was conserved among ATL patients after allo-HSCT. Furthermore, the PDR
Tax
-CTL clones selectively expanded and showed strong cytotoxic activities against HTLV-1. On the other hand, it remains unclear how Tax
-CTL repertoire exists in ACs. In this study, we comprehensively compared Tax-specific TCR repertoires at the single-cell level between ACs and ATL patients. Tax
-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was conserved in all ACs and ATL patients, regardless of clinical subtype in HTLV-1 infection.</abstract><cop>United States</cop><pmid>28724766</pmid><doi>10.1128/JVI.00974-17</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-538X |
| ispartof | Journal of virology, 2017-10, Vol.91 (19) |
| issn | 0022-538X 1098-5514 |
| language | eng |
| recordid | cdi_crossref_primary_10_1128_JVI_00974_17 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Amino Acid Sequence - genetics Antigens, CD7 - metabolism Cell Adhesion Molecule-1 Cell Adhesion Molecules - metabolism Cells, Cultured Gene Products, tax - genetics Gene Products, tax - immunology HLA-A24 Antigen - genetics HLA-A24 Antigen - immunology HTLV-I Infections - pathology HTLV-I Infections - virology Human T-lymphotropic virus 1 - genetics Human T-lymphotropic virus 1 - immunology Humans Immunoglobulins - metabolism Immunologic Memory - immunology Leukemia-Lymphoma, Adult T-Cell - genetics Leukemia-Lymphoma, Adult T-Cell - immunology Receptors, Antigen, T-Cell - genetics Receptors, Antigen, T-Cell - immunology T-Lymphocytes, Cytotoxic - immunology |
| title | A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax 301-309 -Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T02%3A46%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Unique%20T-Cell%20Receptor%20Amino%20Acid%20Sequence%20Selected%20by%20Human%20T-Cell%20Lymphotropic%20Virus%20Type%201%20Tax%20301-309%20-Specific%20Cytotoxic%20T%20Cells%20in%20HLA-A24:02-Positive%20Asymptomatic%20Carriers%20and%20Adult%20T-Cell%20Leukemia/Lymphoma%20Patients&rft.jtitle=Journal%20of%20virology&rft.au=Ishihara,%20Yuko&rft.date=2017-10-01&rft.volume=91&rft.issue=19&rft.issn=0022-538X&rft.eissn=1098-5514&rft_id=info:doi/10.1128/JVI.00974-17&rft_dat=%3Cpubmed_cross%3E28724766%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/28724766&rfr_iscdi=true |