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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by O’Herrin, S. M. Articles by Bluestone, J. A. Search for Related Content PubMed PubMed Citation Articles by O’Herrin, S. M. Articles by Bluestone, J. A.

Antigen-Specific Blockade of T Cells In Vivo Using Dimeric MHC Peptide¹

Sean M. O’Herrin^2,*,, Jill E. Slansky, Q. Tang^*,, Mary A. Markiewicz, Thomas F. Gajewski^*,,, Drew M. Pardoll, Jonathan P. Schneck^3,¶ and Jeffrey A. Bluestone^3,4,*,

^* The Ben May Institute for Cancer Research, Departments of Medicine and Pathology, and Committee on Immunology, University of Chicago, Chicago, IL 60637; and Departments of Oncology and ^¶ Pathology, Johns Hopkins University, Baltimore, MD 21218

Ag-specific immune tolerance in clinical organ transplantation is currently an unrealized but critical goal of transplant biology. The specificity and avidity of multimerized MHC-peptide complexes suggests their potential ability to modulate T cell sensitization and effector functions. In this study, we examined the ability of MHC-peptide dimers to modulate T cell function both in vitro and in vivo. Soluble MHC dimers induced modulation of surface TCR expression and inhibited T cell cytolytic activity at nanomolar concentrations in vitro. Furthermore, engagement of TCR by soluble dimers resulted in phosphorylation of the TCR -chain and recruitment and phosphorylation of -associated protein-70 to the signaling complex, the latter of which increased upon dimer cross-linking. Significantly, Ag-specific inhibition of an alloreactive TCR-transgenic T cell population in vivo resulted in consequent outgrowth of an allogeneic tumor. The prolonged Ag-specific suppression of expansion and/or effector function of cognate T cells in vivo suggests that soluble MHC dimers may be a means of inducing sustained Ag-specific T cell unresponsiveness in vivo.

This article has been cited by other articles:

				G. S. Angelov, P. Guillaume, M. Cebecauer, G. Bosshard, D. Dojcinovic, P. Baumgaertner, and I. F. Luescher Soluble MHC-Peptide Complexes Containing Long Rigid Linkers Abolish CTL-Mediated Cytotoxicity J. Immunol., March 15, 2006; 176(6): 3356 - 3365. [Abstract] [Full Text] [PDF]

				A. Fried, M. Berg, B. Sharma, S. Bonde, and N. Zavazava Recombinant dimeric MHC antigens protect cardiac allografts from rejection and visualize alloreactive T cells J. Leukoc. Biol., September 1, 2005; 78(3): 595 - 604. [Abstract] [Full Text] [PDF]

				M. Cebecauer, P. Guillaume, S. Mark, O. Michielin, N. Boucheron, M. Bezard, B. H. Meyer, J.-M. Segura, H. Vogel, and I. F. Luescher CD8+ Cytotoxic T Lymphocyte Activation by Soluble Major Histocompatibility Complex-Peptide Dimers J. Biol. Chem., June 24, 2005; 280(25): 23820 - 23828. [Abstract] [Full Text] [PDF]

				M. Cebecauer, P. Guillaume, P. Hozak, S. Mark, H. Everett, P. Schneider, and I. F. Luescher Soluble MHC-Peptide Complexes Induce Rapid Death of CD8+ CTL J. Immunol., June 1, 2005; 174(11): 6809 - 6819. [Abstract] [Full Text] [PDF]

				S. Thomas, R. Kumar, A. Preda-Pais, S. Casares, and T.-D. Brumeanu A Model for Antigen-Specific T-Cell Anergy: Displacement of CD4-p56lck Signalosome from the Lipid Rafts by a Soluble, Dimeric Peptide-MHC Class II Chimera J. Immunol., June 15, 2003; 170(12): 5981 - 5992. [Abstract] [Full Text] [PDF]

				L. Zuo, C. M. Cullen, M. L. DeLay, S. Thornton, L. K. Myers, E. F. Rosloniec, G. P. Boivin, and R. Hirsch A Single-Chain Class II MHC-IgG3 Fusion Protein Inhibits Autoimmune Arthritis by Induction of Antigen-Specific Hyporesponsiveness J. Immunol., March 1, 2002; 168(5): 2554 - 2559. [Abstract] [Full Text] [PDF]