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 Daniel, C. Articles by Allen, P. M. Search for Related Content PubMed PubMed Citation Articles by Daniel, C. Articles by Allen, P. M.

Inhibition of an In Vitro CD4⁺ T Cell Alloresponse Using Altered Peptide Ligands¹

Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110

In this study, we explore the potential of altered peptide ligands (APLs) to modulate the alloresponse of CD4⁺ T cells using elements of the murine hemoglobin (Hb) Ag model. We first demonstrated that the T cell 2.102, specific for the Hb(64-76)/I-E^k complex, was alloreactive against splenocytes of the H-2^p haplotype. Using Ab-blocking and transfection experiments, we further showed that this alloreactivity was restricted to the class II molecule I-E^p. We tested a panel of APLs previously shown to antagonize the Hb response of 2.102 and found that these peptides could also effectively inhibit the alloresponse to I-E^p. Importantly, these peptides were able to antagonize the alloresponse of naive T cells derived from mice transgenic for the 2.102 TCR, as well as Th1 and Th2 cell lines. The antagonism required the presence of both I-E^p and I-E^k on the same APC. Our study demonstrates the effectiveness of APLs to antagonize the primary alloresponse of specific T cells and provides a basis for the development of immunotherapeutics for use in transplantation and immune-mediated diseases.

This article has been cited by other articles:

				G. P. Morris and P. M. Allen Cutting Edge: Highly Alloreactive Dual TCR T Cells Play a Dominant Role in Graft-versus-Host Disease J. Immunol., June 1, 2009; 182(11): 6639 - 6643. [Abstract] [Full Text] [PDF]

				K. S. Weber, M. J. Miller, and P. M. Allen Th17 Cells Exhibit a Distinct Calcium Profile from Th1 and Th2 Cells and Have Th1-Like Motility and NF-AT Nuclear Localization J. Immunol., February 1, 2008; 180(3): 1442 - 1450. [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]

				J. Roger, A. Chalifour, S. Lemieux, and P. Duplay Cutting Edge: Ly49A Inhibits TCR/CD3-Induced Apoptosis and IL-2 Secretion J. Immunol., July 1, 2001; 167(1): 6 - 10. [Abstract] [Full Text] [PDF]

				D. J. Becker, R. E. LaPorte, I. Libman, M. Pietropaolo, and H.-M. Dosch Prevention of Type 1 Diabetes: Is Now the Time? J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 498 - 506. [Full Text]

				H. J. Hernandez and M. J. Stadecker Elucidation and Role of Critical Residues of Immunodominant Peptide Associated with T Cell-Mediated Parasitic Disease J. Immunol., October 1, 1999; 163(7): 3877 - 3882. [Abstract] [Full Text] [PDF]

				H. S. de Koster, C. J. Vermeulen, H. S. Hiemstra, R. Amons, J. W. Drijfhout, and F. Koning Definition of agonists and design of antagonists for alloreactive T cell clones using synthetic peptide libraries Int. Immunol., April 1, 1999; 11(4): 585 - 591. [Abstract] [Full Text] [PDF]

				S. R. Burrows, R. Khanna, and D. J. Moss Direct Alloreactivity by Human Cytotoxic T Lymphocytes Can Be Inhibited by Altered Peptide Ligand Antagonism Blood, February 1, 1999; 93(3): 1020 - 1024. [Abstract] [Full Text] [PDF]