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 Thomson, C. T. Articles by Nathenson, S. G. Search for Related Content PubMed PubMed Citation Articles by Thomson, C. T. Articles by Nathenson, S. G.

A Structural Difference Limited to One Residue of the Antigenic Peptide Can Profoundly Alter the Biological Outcome of the TCR-Peptide/MHC Class I Interaction¹

Cole T. Thomson^*, Alexis M. Kalergis, James C. Sacchettini and Stanley G. Nathenson^2,,

Departments of ^* Biochemistry, Microbiology and Immunology, and Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461; and Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843

The vesicular stomatitis virus (VSV) octapeptide RGYVYQGL binds to H-2K^b and triggers a cytotoxic T cell response in mice. A variant peptide, RGYVYEGL (E6) with a glutamic acid for glutamine replacement at position 6 of the VSV peptide, elicits a T cell response with features that are quite different from those elicited by the wild-type VSV peptide. The differences found in the nature of the T cells responding to the E6 peptide include changes in both the V elements and the sequences of the complementarity-determining region 3 loops of their TCRs. Further experiments found that the E6 peptide can act as an antagonist for VSV-specific T cell hybridomas. To determine whether these differences in V usage, complementarity-determining region 3 sequences, and the switch from agonism to antagonism are caused by a conformational change on the MHC, the peptide, or both, we determined the crystal structure of the variant E6 peptide bound to H-2K^b. This structure shows that the only significant structural difference between H-2K^b/E6 and the previously determined H-2K^b/VSV is limited to the side chain of position 6 of the peptide, with no differences in the MHC molecule. Thus, a minor conformational change in the peptide can profoundly alter the biological outcome of the TCR-peptide/MHC interaction.

This article has been cited by other articles:

				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]

				D. M. Gakamsky, I. F. Luescher, and I. Pecht T cell receptor-ligand interactions: A conformational preequilibrium or an induced fit PNAS, June 15, 2004; 101(24): 9063 - 9066. [Abstract] [Full Text] [PDF]

				A. L.-D. de Cerio, J. J. Lasarte, N. Casares, P. Sarobe, M. Ruiz, J. Prieto, and F. Borras-Cuesta Engineering Th determinants for efficient priming of humoral and cytotoxic T cell responses Int. Immunol., June 1, 2003; 15(6): 691 - 699. [Abstract] [Full Text] [PDF]

				K. Nilges, H. Hohn, H. Pilch, C. Neukirch, K. Freitag, P. J. Talbot, and M. J. Maeurer Human Papillomavirus Type 16 E7 Peptide-Directed CD8+ T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein J. Virol., May 1, 2003; 77(9): 5464 - 5474. [Abstract] [Full Text] [PDF]

				W. Zhang, S. Honda, F. Wang, T. P. DiLorenzo, A. M. Kalergis, D. A. Ostrov, and S. G. Nathenson Immunobiological Analysis of TCR Single-Chain Transgenic Mice Reveals New Possibilities for Interaction between CDR3{alpha} and an Antigenic Peptide Bound to MHC Class I J. Immunol., October 15, 2001; 167(8): 4396 - 4404. [Abstract] [Full Text] [PDF]