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 Maile, R. Articles by Frelinger, J. A. Search for Related Content PubMed PubMed Citation Articles by Maile, R. Articles by Frelinger, J. A.

Antigen-Specific Modulation of an Immune Response by In Vivo Administration of Soluble MHC Class I Tetramers¹

Robert Maile^2,*, Bo Wang^*, Wesley Schooler, Anthony Meyer, Edward J. Collins^*, and Jeffrey A. Frelinger^*

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

Soluble MHC/peptide tetramers that can directly bind the TCR allow the direct visualization and quantitation of Ag-specific T cells in vitro and in vivo. We used HY-D^b tetramers to assess the numbers of HY-reactive CD8⁺ T cells in HYTCR-transgenic mice and in naive, wild-type C57BL/6 (B6) mice. As expected, tetramer staining showed the majority of T cells were male-specific CD8⁺ T cells in female HY-TCR mice. Staining of B6 mice showed a small population of male-specific CD8⁺ T cells in female mice. The effect of administration of soluble MHC class I tetramers on CD8⁺ T cell activation in vivo was unknown. Injection of HY-D^b tetramer in vivo effectively primed female mice for a more rapid proliferative response to both HY peptide and male splenocytes. Furthermore, wild-type B6 female mice injected with a single dose of HY-D^b tetramer rejected B6 male skin grafts more rapidly than female littermates treated with irrelevant tetramer. In contrast, multiple doses of HY-D^b tetramer did not further decrease graft survival. Rather, female B6 mice injected with multiple doses of HY-D^b tetramer rejected male skin grafts more slowly than mice primed with a single injection of tetramer or irradiated male spleen cells, suggesting clonal exhaustion or anergy. Our data highlight the ability of soluble MHC tetramers to identify scarce alloreactive T cell populations and the use of such tetramers to directly modulate an Ag-specific T cell response in vivo.

This article has been cited by other articles:

				S. H. Apte, A. Baz, P. Groves, A. Kelso, and N. Kienzle Interferon-{gamma} and interleukin-4 reciprocally regulate CD8 expression in CD8+ T cells PNAS, November 11, 2008; 105(45): 17475 - 17480. [Abstract] [Full Text] [PDF]

				Z. Xiao, M. F. Mescher, and S. C. Jameson Detuning CD8 T cells: down-regulation of CD8 expression, tetramer binding, and response during CTL activation J. Exp. Med., October 29, 2007; 204(11): 2667 - 2677. [Abstract] [Full Text] [PDF]

				P. R. Hess, C. Barnes, M. D. Woolard, M. D. L. Johnson, J. M. Cullen, E. J. Collins, and J. A. Frelinger Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin Blood, April 15, 2007; 109(8): 3300 - 3307. [Abstract] [Full Text] [PDF]

				A. F. M. Maree, P. Santamaria, and L. Edelstein-Keshet Modeling competition among autoreactive CD8+ T cells in autoimmune diabetes: implications for antigen-specific therapy Int. Immunol., July 1, 2006; 18(7): 1067 - 1077. [Abstract] [Full Text] [PDF]

				R. Maile, C. M. Barnes, A. I. Nielsen, A. A. Meyer, J. A. Frelinger, and B. A. Cairns Lymphopenia-Induced Homeostatic Proliferation of CD8+ T Cells Is a Mechanism for Effective Allogeneic Skin Graft Rejection following Burn Injury. J. Immunol., June 1, 2006; 176(11): 6717 - 6726. [Abstract] [Full Text] [PDF]

				J. D. Stone and L. J. Stern CD8 T Cells, Like CD4 T Cells, Are Triggered by Multivalent Engagement of TCRs by MHC-Peptide Ligands but Not by Monovalent Engagement J. Immunol., February 1, 2006; 176(3): 1498 - 1505. [Abstract] [Full Text] [PDF]

				N. J. Felix, A. Suri, J. J. Walters, S. Horvath, M. L. Gross, and P. M. Allen I-Ep-Bound Self-Peptides: Identification, Characterization, and Role in Alloreactivity J. Immunol., January 15, 2006; 176(2): 1062 - 1071. [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]

				T. J. Fry, M. Sinha, M. Milliron, Y.-W. Chu, V. Kapoor, R. E. Gress, E. Thomas, and C. L. Mackall Flt3 ligand enhances thymic-dependent and thymic-independent immune reconstitution Blood, November 1, 2004; 104(9): 2794 - 2800. [Abstract] [Full Text] [PDF]

				R. R. Yuan, P. Wong, M. R. McDevitt, E. Doubrovina, I. Leiner, W. Bornmann, R. O'Reilly, E. G. Pamer, and D. A. Scheinberg Targeted deletion of T-cell clones using alpha-emitting suicide MHC tetramers Blood, October 15, 2004; 104(8): 2397 - 2402. [Abstract] [Full Text] [PDF]

				K. L. Mueller, M. A. Daniels, A. Felthauser, C. Kao, S. C. Jameson, and Y. Shimizu Cutting Edge: LFA-1 Integrin-Dependent T Cell Adhesion Is Regulated by Both Ag Specificity and Sensitivity J. Immunol., August 15, 2004; 173(4): 2222 - 2226. [Abstract] [Full Text] [PDF]

				J. Stebbing, B. Gazzard, S. Patterson, M. Bower, D. Perumal, M. Nelson, A. McMichael, G. Ogg, A. Epenetos, F. Gotch, et al. Antibody-targeted MHC complex-directed expansion of HIV-1- and KSHV-specific CD8+ lymphocytes: a new approach to therapeutic vaccination Blood, March 1, 2004; 103(5): 1791 - 1795. [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]

				L. Lybarger, Y. Y. L. Yu, M. J. Miley, D. H. Fremont, N. Myers, T. Primeau, S. M. Truscott, J. M. Connolly, and T. H. Hansen Enhanced Immune Presentation of a Single-chain Major Histocompatibility Complex Class I Molecule Engineered to Optimize Linkage of a C-terminally Extended Peptide J. Biol. Chem., July 11, 2003; 278(29): 27105 - 27111. [Abstract] [Full Text] [PDF]

				F. Buseyne, D. Scott-Algara, F. Porrot, B. Corre, N. Bellal, M. Burgard, C. Rouzioux, S. Blanche, and Y. Riviere Frequencies of Ex Vivo-Activated Human Immunodeficiency Virus Type 1-Specific Gamma-Interferon-Producing CD8+ T Cells in Infected Children Correlate Positively with Plasma Viral Load J. Virol., November 13, 2002; 76(24): 12414 - 12422. [Abstract] [Full Text] [PDF]

				Q. Ge, J. D. Stone, M. T. Thompson, J. R. Cochran, M. Rushe, H. N. Eisen, J. Chen, and L. J. Stern Soluble peptide-MHC monomers cause activation of CD8+ T cells through transfer of the peptide to T cell MHC molecules PNAS, October 15, 2002; 99(21): 13729 - 13734. [Abstract] [Full Text] [PDF]