Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor ζ chain ITAMs and their tyrosine residues

Wook Jin Chae, Heung Kyu Lee, Jin Hwan Han, Sang Won Vincent Kim, Afred L.M. Bothwell, Tomohiro Morio, Sang Kyou Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The issue of whether three ITAMs in the TCR ζ chain can transmit qualitatively distinct signals or redundantly amplify TCR-mediated activation signals was extensively investigated using stable hCD8-ζ Jurkat transfectants which contain stepwise deletions of each ITAM or mutations of tyrosine residues in each ITAM of TCR ζ chain. The influence of mutations of each tyrosine residue on reduction of the amount and species of tyrosine phosphorylated proteins recruited to ζ chain was quite distinctive, but they were roughly proportional to the number of functionally intact ITAMs. However, the first N-terminal ITAM had a signaling potential to trigger most intracellular signaling events for T cell activation and apoptosis similar to wild-type CD8-ζ, but this level was substantially reduced in the presence of the first and second N-terminal ITAM together. Mutations of tyrosine residues in first and second N-terminal ITAM significantly impaired most signaling events leading to T cell activation and activation-induced cell death, but phosphorylation of mitogen-activated protein kinases (MAPKs) was differentially impaired in each mutant. The mutation of the first tyrosine residue in C-terminal ITAM did not show any impairment in induction of surface antigens and cell death, but rather increased IL-2 secretion and MAPK phosphorylation. Therefore, in this study we demonstrated that the ITAMs and their tyrosine residues of TCR ζ chain can transmit qualitatively differential intracellular signals upon TCR stimulation through distinctive regulation of recruitment of tyrosine phosphorylated proteins to ζ chain and activation of various MAPKs.

Original languageEnglish
Pages (from-to)1225-1236
Number of pages12
JournalInternational Immunology
Volume16
Issue number9
DOIs
Publication statusPublished - 2004 Sep 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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