Molecular characterization of T cell receptors and non-MHC restricted T cell receptor binding peptides

Persistent Link:
http://hdl.handle.net/10150/284969
Title:
Molecular characterization of T cell receptors and non-MHC restricted T cell receptor binding peptides
Author:
Im, Jin Seon
Issue Date:
1999
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
T cells recognize antigenic peptides presented by MHC molecules on antigen presenting cells (APC) through T cell receptors (TCRs). Since TCRs are very similar to antibodies in structure and genetics, TCRs might have the potential to bind free antigens as antibodies do. Here, peptides which bound TCRs irrespective of MHC molecules have been identified by screening "one-bead one-peptide" combinatorial libraries. Peptides: VRENAR, RTGNYV, GKMHFK, KDAVKR and RKPQAI bound recombinant Jurkat single chain T cell receptors (scTcrs). GKMHFK, KDAVKR and RKPQAI were also specific for natural TCRs on the Jurkat cell surface. Molecular modeling implies that Glu96 in the CDR3 loop of TCR alpha chain is a candidate for the peptide interaction site. However, TCR-binding peptides did not induce biological effects on parental Jurkat cells. To extend this study to a biologically relevant system, diabetogenic T cells involved in insulin-dependent diabetes mellitus (IDDM) have been characterized. GAD(524-543) responding T cells showed restricted TCR variable gene usage, which utilized preferentially Vα17 and Vβ12. Three domain single chain T cell receptors (3D scTcr) were constructed as tools to investigate potential therapies for IDDM and to identify peptides which bind to TCR without association of MHC molecules. Functional analysis has demonstrated that GAD(524-543)-specific scTcrs retained the ability to bind GAD(524-543)/IAg7 complex. This work shows that recombinant scTcrs can bind cognate peptide presented by MHC molecules, therefore they can be used as substitutes for natural TCRs in screening "one-bead one-peptide" combinatorial libraries to identify TCR-binding peptide.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Immunology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Microbiology and Immunology
Degree Grantor:
University of Arizona
Advisor:
Lake, Douglas F.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleMolecular characterization of T cell receptors and non-MHC restricted T cell receptor binding peptidesen_US
dc.creatorIm, Jin Seonen_US
dc.contributor.authorIm, Jin Seonen_US
dc.date.issued1999en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractT cells recognize antigenic peptides presented by MHC molecules on antigen presenting cells (APC) through T cell receptors (TCRs). Since TCRs are very similar to antibodies in structure and genetics, TCRs might have the potential to bind free antigens as antibodies do. Here, peptides which bound TCRs irrespective of MHC molecules have been identified by screening "one-bead one-peptide" combinatorial libraries. Peptides: VRENAR, RTGNYV, GKMHFK, KDAVKR and RKPQAI bound recombinant Jurkat single chain T cell receptors (scTcrs). GKMHFK, KDAVKR and RKPQAI were also specific for natural TCRs on the Jurkat cell surface. Molecular modeling implies that Glu96 in the CDR3 loop of TCR alpha chain is a candidate for the peptide interaction site. However, TCR-binding peptides did not induce biological effects on parental Jurkat cells. To extend this study to a biologically relevant system, diabetogenic T cells involved in insulin-dependent diabetes mellitus (IDDM) have been characterized. GAD(524-543) responding T cells showed restricted TCR variable gene usage, which utilized preferentially Vα17 and Vβ12. Three domain single chain T cell receptors (3D scTcr) were constructed as tools to investigate potential therapies for IDDM and to identify peptides which bind to TCR without association of MHC molecules. Functional analysis has demonstrated that GAD(524-543)-specific scTcrs retained the ability to bind GAD(524-543)/IAg7 complex. This work shows that recombinant scTcrs can bind cognate peptide presented by MHC molecules, therefore they can be used as substitutes for natural TCRs in screening "one-bead one-peptide" combinatorial libraries to identify TCR-binding peptide.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Immunology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLake, Douglas F.en_US
dc.identifier.proquest9946819en_US
dc.identifier.bibrecord.b39915554en_US
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