Characterization of signal transduction through the TCR-ζ chain following T cell stimulation with analogue peptides of type II collagen 260- 267

Bo Tang, Linda Myers, Edward F. Rosloniec, Karen B. Whittington, John Stuart, Andrew Kang

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Abstract

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 to TCR-ζ 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-ζ to either partial or a complete abrogation of phosphorylation. Critical substitutions also completely abrogated the phosphorylation of ZAP70, a downstream molecule in TCR-ζ 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-ζ and the amount of cytokine induced. Selected analogue peptides were tested as tolerogens in neonatal mice. Analogues that did not induce the phosphorylation of ζ chain, such as B3 (CII 251-270s263F→N), were completely unable to induce tolerance, while analogues that caused a partial phosphorylation, such as B6 (CII 251- 270s267Q→T) and A3 (CII 245-270s269P→A), 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.

Original languageEnglish (US)
Pages (from-to)3135-3142
Number of pages8
JournalJournal of Immunology
Volume160
Issue number7
StatePublished - Apr 1 1998

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Collagen Type II
Signal Transduction
Phosphorylation
T-Lymphocytes
Peptides
Hybridomas
Cytokines
Arthritis
Amino Acids
Inbred DBA Mouse
Tyrosine

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Characterization of signal transduction through the TCR-ζ chain following T cell stimulation with analogue peptides of type II collagen 260- 267. / Tang, Bo; Myers, Linda; Rosloniec, Edward F.; Whittington, Karen B.; Stuart, John; Kang, Andrew.

In: Journal of Immunology, Vol. 160, No. 7, 01.04.1998, p. 3135-3142.

Research output: Contribution to journalArticle

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