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 Tang, B. Articles by Kang, A. H. Search for Related Content PubMed PubMed Citation Articles by Tang, B. Articles by Kang, A. H.

Characterization of Signal Transduction Through the TCR- Chain Following T Cell Stimulation with Analogue Peptides of Type II Collagen 260–267¹

Bo Tang^2,*, Linda K. Myers, Edward F. Rosloniec^*,, Karen B. Whittington, John M. Stuart^*, and Andrew H. Kang^*,

Departments of ^* Medicine and Pediatrics, University of Tennessee, Memphis, TN 38163; and Veterans Affairs Medical Center, Memphis, TN 38104

The immunodominant T cell determinant of type II collagen (CII) recognized by DBA/1 mice (I-A^q) is CII 260–267. The aims of this study were to determine the role of the amino acid residues within CII 245–270 in T cell signal transduction. To that end, we utilized I-A^q-restricted, CII-specific T cell hybridomas and examined tyrosine phosphorylation of TCR- following stimulation with either wild-type CII 245–270 or a panel of analogue peptides. A variety of patterns occurred, ranging from increased phosphorylation of TCR- to either partial or a complete abrogation of phosphorylation. Critical substitutions also completely abrogated the phosphorylation of ZAP70, a downstream molecule in TCR- signaling. Evaluation of the supernatants of the T cell hybridomas for cytokine production in response to the peptides revealed a close correlation between the induction of phosphorylation of TCR- and the amount of cytokine induced. Selected analogue peptides were tested as tolerogens in neonatal mice. Analogues that did not induce the phosphorylation of chain, such as B3 (CII 251–270s263FN), were completely unable to induce tolerance, while analogues that caused a partial phosphorylation, such as B6 (CII 251–270s267QT) and A3 (CII 245–270s269PA), induced partial tolerance judged by intermediate degrees of suppression of arthritis. We conclude that discrete alterations in specific amino acid residues of antigenic peptides had profound effects on T cell signaling and that the signaling correlated with T cell cytokine secretion and T cell function in the induction of tolerance and suppression of arthritis.

This article has been cited by other articles:

				B. Dzhambazov, K. S. Nandakumar, J. Kihlberg, L. Fugger, R. Holmdahl, and M. Vestberg Therapeutic Vaccination of Active Arthritis with a Glycosylated Collagen Type II Peptide in Complex with MHC Class II Molecules J. Immunol., February 1, 2006; 176(3): 1525 - 1533. [Abstract] [Full Text] [PDF]

				L. Bouhdoud, P. Villain, A. Merzouki, M. Arella, and C. Couture T-Cell Receptor-Mediated Anergy of a Human Immunodeficiency Virus (HIV) gp120-Specific CD4+ Cytotoxic T-Cell Clone, Induced by a Natural HIV Type 1 Variant Peptide J. Virol., March 1, 2000; 74(5): 2121 - 2130. [Abstract] [Full Text]

				C. Maccalli, P. Pisarra, C. Vegetti, M. Sensi, G. Parmiani, and A. Anichini Differential Loss of T Cell Signaling Molecules in Metastatic Melanoma Patients' T Lymphocyte Subsets Expressing Distinct TCR Variable Regions J. Immunol., December 15, 1999; 163(12): 6912 - 6923. [Abstract] [Full Text] [PDF]

				L. K. Myers, B. Tang, E. F. Rosloniec, J. M. Stuart, T. M. Chiang, and A. H. Kang Characterization of a Peptide Analog of a Determinant of Type II Collagen That Suppresses Collagen-Induced Arthritis J. Immunol., October 1, 1998; 161(7): 3589 - 3595. [Abstract] [Full Text] [PDF]