Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes

Autores
McCormick, John K.; Tripp, Timothy J.; Llera, Andrea Sabina; Sundberg, Eric J.; Dinges, Martin M.; Mariuzza, Roy A.; Schlievert, Patrick M.
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Superantigens (SAGs) aberrantly alter immune system function through simultaneous interaction with lateral surfaces of MHC class II molecules on APCs and with particular variable regions of the TCR beta-chain (Vbeta). To further define the interface between the bacterial SAG toxic shock syndrome toxin-1 (TSST-1) and the TCR, we performed alanine scanning mutagenesis within the putative TCR binding region of TSST-1 along the central alpha helix adjacent to the N-terminal alpha helix and the beta7-beta9 loop as well as with two universally conserved SAG residues (Leu(137) and Tyr(144) in TSST-1). Mutants were analyzed for multiple functional activities, and various residues appeared to play minor or insignificant roles in the TCR interaction. The locations of six residues (Gly(16), Trp(116), Glu(132), His(135), Gln(136), and Gln(139)), each individually critical for functional activity as well as direct interaction with the human TCR Vbeta2.1-chain, indicate that the interface occurs in a novel region of the SAG molecule. Based on these data, a model of the MHC/TSST-1/TCR ternary complex predicts similarities seen with other characterized SAGs, although the CDR3 loop of Vbeta2.1 is probably involved in direct SAG-TCR molecular interactions, possibly contributing to the TCR Vbeta specificity of TSST-1.
Fil: McCormick, John K.. University of Minnesota; Estados Unidos
Fil: Tripp, Timothy J.. University of Minnesota; Estados Unidos
Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of Maryland; Estados Unidos
Fil: Sundberg, Eric J.. University of Maryland; Estados Unidos
Fil: Dinges, Martin M.. University of Minnesota; Estados Unidos
Fil: Mariuzza, Roy A.. University of Maryland; Estados Unidos
Fil: Schlievert, Patrick M.. University of Minnesota; Estados Unidos
Materia
Tcr Receptor
Superantigens
Major Histocompatibility Complex
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/43551

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network_name_str CONICET Digital (CONICET)
spelling Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary ComplexesMcCormick, John K.Tripp, Timothy J.Llera, Andrea SabinaSundberg, Eric J.Dinges, Martin M.Mariuzza, Roy A.Schlievert, Patrick M.Tcr ReceptorSuperantigensMajor Histocompatibility Complexhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Superantigens (SAGs) aberrantly alter immune system function through simultaneous interaction with lateral surfaces of MHC class II molecules on APCs and with particular variable regions of the TCR beta-chain (Vbeta). To further define the interface between the bacterial SAG toxic shock syndrome toxin-1 (TSST-1) and the TCR, we performed alanine scanning mutagenesis within the putative TCR binding region of TSST-1 along the central alpha helix adjacent to the N-terminal alpha helix and the beta7-beta9 loop as well as with two universally conserved SAG residues (Leu(137) and Tyr(144) in TSST-1). Mutants were analyzed for multiple functional activities, and various residues appeared to play minor or insignificant roles in the TCR interaction. The locations of six residues (Gly(16), Trp(116), Glu(132), His(135), Gln(136), and Gln(139)), each individually critical for functional activity as well as direct interaction with the human TCR Vbeta2.1-chain, indicate that the interface occurs in a novel region of the SAG molecule. Based on these data, a model of the MHC/TSST-1/TCR ternary complex predicts similarities seen with other characterized SAGs, although the CDR3 loop of Vbeta2.1 is probably involved in direct SAG-TCR molecular interactions, possibly contributing to the TCR Vbeta specificity of TSST-1.Fil: McCormick, John K.. University of Minnesota; Estados UnidosFil: Tripp, Timothy J.. University of Minnesota; Estados UnidosFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of Maryland; Estados UnidosFil: Sundberg, Eric J.. University of Maryland; Estados UnidosFil: Dinges, Martin M.. University of Minnesota; Estados UnidosFil: Mariuzza, Roy A.. University of Maryland; Estados UnidosFil: Schlievert, Patrick M.. University of Minnesota; Estados UnidosAmerican Association of Immunologists2003-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/43551McCormick, John K.; Tripp, Timothy J.; Llera, Andrea Sabina; Sundberg, Eric J.; Dinges, Martin M.; et al.; Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes; American Association of Immunologists; Journal of Immunology; 171; 3; 7-2003; 1385-13920022-17671550-6606CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/171/3/1385.longinfo:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.171.3.1385info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:31Zoai:ri.conicet.gov.ar:11336/43551instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:57:31.75CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes
title Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes
spellingShingle Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes
McCormick, John K.
Tcr Receptor
Superantigens
Major Histocompatibility Complex
title_short Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes
title_full Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes
title_fullStr Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes
title_full_unstemmed Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes
title_sort Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes
dc.creator.none.fl_str_mv McCormick, John K.
Tripp, Timothy J.
Llera, Andrea Sabina
Sundberg, Eric J.
Dinges, Martin M.
Mariuzza, Roy A.
Schlievert, Patrick M.
author McCormick, John K.
author_facet McCormick, John K.
Tripp, Timothy J.
Llera, Andrea Sabina
Sundberg, Eric J.
Dinges, Martin M.
Mariuzza, Roy A.
Schlievert, Patrick M.
author_role author
author2 Tripp, Timothy J.
Llera, Andrea Sabina
Sundberg, Eric J.
Dinges, Martin M.
Mariuzza, Roy A.
Schlievert, Patrick M.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Tcr Receptor
Superantigens
Major Histocompatibility Complex
topic Tcr Receptor
Superantigens
Major Histocompatibility Complex
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Superantigens (SAGs) aberrantly alter immune system function through simultaneous interaction with lateral surfaces of MHC class II molecules on APCs and with particular variable regions of the TCR beta-chain (Vbeta). To further define the interface between the bacterial SAG toxic shock syndrome toxin-1 (TSST-1) and the TCR, we performed alanine scanning mutagenesis within the putative TCR binding region of TSST-1 along the central alpha helix adjacent to the N-terminal alpha helix and the beta7-beta9 loop as well as with two universally conserved SAG residues (Leu(137) and Tyr(144) in TSST-1). Mutants were analyzed for multiple functional activities, and various residues appeared to play minor or insignificant roles in the TCR interaction. The locations of six residues (Gly(16), Trp(116), Glu(132), His(135), Gln(136), and Gln(139)), each individually critical for functional activity as well as direct interaction with the human TCR Vbeta2.1-chain, indicate that the interface occurs in a novel region of the SAG molecule. Based on these data, a model of the MHC/TSST-1/TCR ternary complex predicts similarities seen with other characterized SAGs, although the CDR3 loop of Vbeta2.1 is probably involved in direct SAG-TCR molecular interactions, possibly contributing to the TCR Vbeta specificity of TSST-1.
Fil: McCormick, John K.. University of Minnesota; Estados Unidos
Fil: Tripp, Timothy J.. University of Minnesota; Estados Unidos
Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. University of Maryland; Estados Unidos
Fil: Sundberg, Eric J.. University of Maryland; Estados Unidos
Fil: Dinges, Martin M.. University of Minnesota; Estados Unidos
Fil: Mariuzza, Roy A.. University of Maryland; Estados Unidos
Fil: Schlievert, Patrick M.. University of Minnesota; Estados Unidos
description Superantigens (SAGs) aberrantly alter immune system function through simultaneous interaction with lateral surfaces of MHC class II molecules on APCs and with particular variable regions of the TCR beta-chain (Vbeta). To further define the interface between the bacterial SAG toxic shock syndrome toxin-1 (TSST-1) and the TCR, we performed alanine scanning mutagenesis within the putative TCR binding region of TSST-1 along the central alpha helix adjacent to the N-terminal alpha helix and the beta7-beta9 loop as well as with two universally conserved SAG residues (Leu(137) and Tyr(144) in TSST-1). Mutants were analyzed for multiple functional activities, and various residues appeared to play minor or insignificant roles in the TCR interaction. The locations of six residues (Gly(16), Trp(116), Glu(132), His(135), Gln(136), and Gln(139)), each individually critical for functional activity as well as direct interaction with the human TCR Vbeta2.1-chain, indicate that the interface occurs in a novel region of the SAG molecule. Based on these data, a model of the MHC/TSST-1/TCR ternary complex predicts similarities seen with other characterized SAGs, although the CDR3 loop of Vbeta2.1 is probably involved in direct SAG-TCR molecular interactions, possibly contributing to the TCR Vbeta specificity of TSST-1.
publishDate 2003
dc.date.none.fl_str_mv 2003-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/43551
McCormick, John K.; Tripp, Timothy J.; Llera, Andrea Sabina; Sundberg, Eric J.; Dinges, Martin M.; et al.; Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes; American Association of Immunologists; Journal of Immunology; 171; 3; 7-2003; 1385-1392
0022-1767
1550-6606
CONICET Digital
CONICET
url http://hdl.handle.net/11336/43551
identifier_str_mv McCormick, John K.; Tripp, Timothy J.; Llera, Andrea Sabina; Sundberg, Eric J.; Dinges, Martin M.; et al.; Functional Analysis of the TCR Binding Domain of Toxic Shock Syndrome Toxin-1 Predicts Further Diversity in MHC Class II/Superantigen/TCR Ternary Complexes; American Association of Immunologists; Journal of Immunology; 171; 3; 7-2003; 1385-1392
0022-1767
1550-6606
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/171/3/1385.long
info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.171.3.1385
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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