HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, B. Articles by Frelinger, J. A. Search for Related Content PubMed PubMed Citation Articles by Wang, B. Articles by Frelinger, J. A.

Peptidic Termini Play a Significant Role in TCR Recognition¹

Bo Wang^2,*, Ashawni Sharma^2,*, Robert Maile^*, Mohamed Saad^*, Edward J. Collins^*, and Jeffrey A. Frelinger^3,*

Departments of ^* Microbiology and Immunology and Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599

TCR recognition of class I MHC is dependent on the composition of the antigenic peptide and the MHC. Single amino acid substitutions in either the MHC or the peptide may dramatically alter recognition. While the major interactions between TCR and the peptide/MHC complex appear to be focused on the complementarity-determining region (CDR)3, it is also clear from the cocrystal structure of class I MHC and TCR that the amino and carboxyl ends of the peptide may play a role through interactions with the CDR1. In this work we show that gp33 variants substituted at the peptidic termini at the putative CDR1 contact regions show improved recognition in B6 mice. The rank order of recognition is different using the P14 transgenic T cells, suggesting that one reason for improved recognition is a change in the TCR repertoire that recognizes the peptide. However, the affinity of the TCR by some of the peptide/MHC complex with increased recognition is improved, as shown by increased tetramer binding to P14 T cells. These substitutions at the termini of the peptide-binding cleft cause localized conformational changes as seen by changes in mAb binding and crystallographic structures. The different peptide structures also show different conformations in the center of the peptide, but these are shown to be energetically similar and thus most likely have no significance with respect to TCR recognition. Therefore, small conformational changes, localized to the CDR1 contact regions, may play a significant role in TCR recognition.

This article has been cited by other articles:

				S. Tian, R. Maile, E. J. Collins, and J. A. Frelinger CD8+ T Cell Activation Is Governed by TCR-Peptide/MHC Affinity, Not Dissociation Rate J. Immunol., September 1, 2007; 179(5): 2952 - 2960. [Abstract] [Full Text] [PDF]

				J. Racape, F. Connan, J. Hoebeke, J. Choppin, and J.-G. Guillet Influence of dominant HIV-1 epitopes on HLA-A3/peptide complex formation PNAS, November 28, 2006; 103(48): 18208 - 18213. [Abstract] [Full Text] [PDF]

				C. Ferreira, A. Furmanski, M. Millrain, I. Bartok, P. Guillaume, R. Lees, E. Simpson, H. R. MacDonald, and J. Dyson TCR-{alpha} CDR3 Loop Audition Regulates Positive Selection J. Immunol., August 15, 2006; 177(4): 2477 - 2485. [Abstract] [Full Text] [PDF]

				J.-L. Chen, G. Stewart-Jones, G. Bossi, N. M. Lissin, L. Wooldridge, E. M. L. Choi, G. Held, P. R. Dunbar, R. M. Esnouf, M. Sami, et al. Structural and kinetic basis for heightened immunogenicity of T cell vaccines J. Exp. Med., April 18, 2005; 201(8): 1243 - 1255. [Abstract] [Full Text] [PDF]

				R. Maile, C. A. Siler, S. E. Kerry, K. E. Midkiff, E. J. Collins, and J. A. Frelinger Peripheral "CD8 Tuning" Dynamically Modulates the Size and Responsiveness of an Antigen-Specific T Cell Pool In Vivo J. Immunol., January 15, 2005; 174(2): 619 - 627. [Abstract] [Full Text] [PDF]

				M. J. Miley, I. Messaoudi, B. M. Metzner, Y. Wu, J. Nikolich-Zugich, and D. H. Fremont Structural Basis for the Restoration of TCR Recognition of an MHC Allelic Variant by Peptide Secondary Anchor Substitution J. Exp. Med., December 6, 2004; 200(11): 1445 - 1454. [Abstract] [Full Text] [PDF]

				M. Fridkis-Hareli, P. A. Reche, and E. L. Reinherz Peptide Variants of Viral CTL Epitopes Mediate Positive Selection and Emigration of Ag-Specific Thymocytes In Vivo J. Immunol., July 15, 2004; 173(2): 1140 - 1150. [Abstract] [Full Text] [PDF]

				L. M. Velloso, J. Michaelsson, H.-G. Ljunggren, G. Schneider, and A. Achour Determination of Structural Principles Underlying Three Different Modes of Lymphocytic Choriomeningitis Virus Escape from CTL Recognition J. Immunol., May 1, 2004; 172(9): 5504 - 5511. [Abstract] [Full Text] [PDF]

				S. E. Kerry, J. Buslepp, L. A. Cramer, R. Maile, L. L. Hensley, A. I. Nielsen, P. Kavathas, B. J. Vilen, E. J. Collins, and J. A. Frelinger Interplay between TCR Affinity and Necessity of Coreceptor Ligation: High-Affinity Peptide-MHC/TCR Interaction Overcomes Lack of CD8 Engagement J. Immunol., November 1, 2003; 171(9): 4493 - 4503. [Abstract] [Full Text] [PDF]