Inhibition of EBV-Induced Lymphoproliferation by CD4+ T Cells Specific for an MHC Class II Promiscuous Epitope
Posttransplant lymphoproliferative disorder (PTLD) and B cell lymphomas induced by EBV continue to be a major life-threatening complication in transplant patients. The establishment and enhancement of T cell immunity to EBV before transplantation and immunosuppressive therapy could help diminish the...
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Veröffentlicht in: | The Journal of immunology (1950) 2002-08, Vol.169 (4), p.2172-2179 |
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creator | Omiya, Ryusuke Buteau, Chantal Kobayashi, Hiroya Paya, Carlos V Celis, Esteban |
description | Posttransplant lymphoproliferative disorder (PTLD) and B cell lymphomas induced by EBV continue to be a major life-threatening complication in transplant patients. The establishment and enhancement of T cell immunity to EBV before transplantation and immunosuppressive therapy could help diminish these complications, but the lack of an effective vaccine has limited this prophylactic approach. We describe here the identification of a peptide epitope from the EBV EBNA2 Ag that is capable of inducing in vitro CD4(+) T cell responses that inhibit the EBV-mediated B lymphocyte proliferation associated with PTLD. Most significantly, T cell responses to the EBNA2 epitope were found to be restricted by numerous MHC class II alleles (DR1, DR7, DR16, DR52, DQ2, and DQ7), indicating that this peptide is highly promiscuous and would be recognized by a large proportion (>50%) of the general population. These results are relevant for the design of a simple, inexpensive and widely applicable peptide-based vaccine to prevent PTLD in solid organ transplant patients. |
doi_str_mv | 10.4049/jimmunol.169.4.2172 |
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The establishment and enhancement of T cell immunity to EBV before transplantation and immunosuppressive therapy could help diminish these complications, but the lack of an effective vaccine has limited this prophylactic approach. We describe here the identification of a peptide epitope from the EBV EBNA2 Ag that is capable of inducing in vitro CD4(+) T cell responses that inhibit the EBV-mediated B lymphocyte proliferation associated with PTLD. Most significantly, T cell responses to the EBNA2 epitope were found to be restricted by numerous MHC class II alleles (DR1, DR7, DR16, DR52, DQ2, and DQ7), indicating that this peptide is highly promiscuous and would be recognized by a large proportion (>50%) of the general population. 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The establishment and enhancement of T cell immunity to EBV before transplantation and immunosuppressive therapy could help diminish these complications, but the lack of an effective vaccine has limited this prophylactic approach. We describe here the identification of a peptide epitope from the EBV EBNA2 Ag that is capable of inducing in vitro CD4(+) T cell responses that inhibit the EBV-mediated B lymphocyte proliferation associated with PTLD. Most significantly, T cell responses to the EBNA2 epitope were found to be restricted by numerous MHC class II alleles (DR1, DR7, DR16, DR52, DQ2, and DQ7), indicating that this peptide is highly promiscuous and would be recognized by a large proportion (>50%) of the general population. These results are relevant for the design of a simple, inexpensive and widely applicable peptide-based vaccine to prevent PTLD in solid organ transplant patients.</description><subject>Antigen-Presenting Cells - immunology</subject><subject>Antigens, Viral - metabolism</subject><subject>B-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>Cell Line</subject><subject>Cytotoxicity, Immunologic</subject><subject>Epitopes - metabolism</subject><subject>Epstein-Barr Virus Nuclear Antigens - immunology</subject><subject>Herpesvirus 4, Human - immunology</subject><subject>Herpesvirus 4, Human - pathogenicity</subject><subject>Histocompatibility Antigens Class II - metabolism</subject><subject>Humans</subject><subject>Lymphocyte Activation</subject><subject>Lymphoma, B-Cell - etiology</subject><subject>Lymphoma, B-Cell - immunology</subject><subject>Lymphoma, B-Cell - prevention & control</subject><subject>Lymphoproliferative Disorders - etiology</subject><subject>Lymphoproliferative Disorders - immunology</subject><subject>Lymphoproliferative Disorders - prevention & control</subject><subject>Organ Transplantation - adverse effects</subject><subject>Viral Proteins</subject><subject>Viral Vaccines - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkF1L8zAAhYMoOqe_QHjJlV5IZ77bXr7WqYWJgh-3Ic0SF2mbmqyM_Xs7N9Grc_Ocw-EB4AyjCUMsv_pwTdO3vp5gkU_YhOCU7IER5hwlQiCxD0YIEZLgVKRH4DjGD4SQQIQdgiNMsOCcpSPQlu3CVW7pfAu9hdPrt6Rs5702czhbN93Cd8HXzpqgvpFqDYsbdglfYGHqOsLnzmhnnYbWB6ha-HBfwKJWMcKyhE_BNy7q3vcRTju39J05AQdW1dGc7nIMXm-nL8V9Mnu8K4v_s0TTNFsm1lJjLcmFoJkWFbGWsUpxS4iyOs2QFqwyVORUaZJRTBXPcM64zYRBSnFDx-B8uzvc_-xNXMrNk-Gyas1wR6Y4zzgemmNAt6AOPsZgrOyCa1RYS4zkRrP80SwHzZLJjeah9W8331eNmf92dl4H4GILLNz7YuWCkbFRdT3gWK5Wqz9TX56PiGI</recordid><startdate>20020815</startdate><enddate>20020815</enddate><creator>Omiya, Ryusuke</creator><creator>Buteau, Chantal</creator><creator>Kobayashi, Hiroya</creator><creator>Paya, Carlos V</creator><creator>Celis, Esteban</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>7X8</scope></search><sort><creationdate>20020815</creationdate><title>Inhibition of EBV-Induced Lymphoproliferation by CD4+ T Cells Specific for an MHC Class II Promiscuous Epitope</title><author>Omiya, Ryusuke ; Buteau, Chantal ; Kobayashi, Hiroya ; Paya, Carlos V ; Celis, Esteban</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-ff3eff296638c6b2ff44ba5f22afc780c64be3693ac28313a581945f86e0aa5e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Antigen-Presenting Cells - immunology</topic><topic>Antigens, Viral - metabolism</topic><topic>B-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>Cell Line</topic><topic>Cytotoxicity, Immunologic</topic><topic>Epitopes - metabolism</topic><topic>Epstein-Barr Virus Nuclear Antigens - immunology</topic><topic>Herpesvirus 4, Human - immunology</topic><topic>Herpesvirus 4, Human - pathogenicity</topic><topic>Histocompatibility Antigens Class II - metabolism</topic><topic>Humans</topic><topic>Lymphocyte Activation</topic><topic>Lymphoma, B-Cell - etiology</topic><topic>Lymphoma, B-Cell - immunology</topic><topic>Lymphoma, B-Cell - prevention & control</topic><topic>Lymphoproliferative Disorders - etiology</topic><topic>Lymphoproliferative Disorders - immunology</topic><topic>Lymphoproliferative Disorders - prevention & control</topic><topic>Organ Transplantation - adverse effects</topic><topic>Viral Proteins</topic><topic>Viral Vaccines - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Omiya, Ryusuke</creatorcontrib><creatorcontrib>Buteau, Chantal</creatorcontrib><creatorcontrib>Kobayashi, Hiroya</creatorcontrib><creatorcontrib>Paya, Carlos V</creatorcontrib><creatorcontrib>Celis, Esteban</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Omiya, Ryusuke</au><au>Buteau, Chantal</au><au>Kobayashi, Hiroya</au><au>Paya, Carlos V</au><au>Celis, Esteban</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of EBV-Induced Lymphoproliferation by CD4+ T Cells Specific for an MHC Class II Promiscuous Epitope</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2002-08-15</date><risdate>2002</risdate><volume>169</volume><issue>4</issue><spage>2172</spage><epage>2179</epage><pages>2172-2179</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Posttransplant lymphoproliferative disorder (PTLD) and B cell lymphomas induced by EBV continue to be a major life-threatening complication in transplant patients. The establishment and enhancement of T cell immunity to EBV before transplantation and immunosuppressive therapy could help diminish these complications, but the lack of an effective vaccine has limited this prophylactic approach. We describe here the identification of a peptide epitope from the EBV EBNA2 Ag that is capable of inducing in vitro CD4(+) T cell responses that inhibit the EBV-mediated B lymphocyte proliferation associated with PTLD. Most significantly, T cell responses to the EBNA2 epitope were found to be restricted by numerous MHC class II alleles (DR1, DR7, DR16, DR52, DQ2, and DQ7), indicating that this peptide is highly promiscuous and would be recognized by a large proportion (>50%) of the general population. 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subjects | Antigen-Presenting Cells - immunology Antigens, Viral - metabolism B-Lymphocytes - immunology CD4-Positive T-Lymphocytes - immunology Cell Line Cytotoxicity, Immunologic Epitopes - metabolism Epstein-Barr Virus Nuclear Antigens - immunology Herpesvirus 4, Human - immunology Herpesvirus 4, Human - pathogenicity Histocompatibility Antigens Class II - metabolism Humans Lymphocyte Activation Lymphoma, B-Cell - etiology Lymphoma, B-Cell - immunology Lymphoma, B-Cell - prevention & control Lymphoproliferative Disorders - etiology Lymphoproliferative Disorders - immunology Lymphoproliferative Disorders - prevention & control Organ Transplantation - adverse effects Viral Proteins Viral Vaccines - immunology |
title | Inhibition of EBV-Induced Lymphoproliferation by CD4+ T Cells Specific for an MHC Class II Promiscuous Epitope |
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