International Immunology Advance Access originally published online on August 9, 2004
International Immunology 2004 16(9):1225-1236; doi:10.1093/intimm/dxh120
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© 2004 The Japanese Society for Immunology
Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor
chain ITAMs and their tyrosine residues
1 Department of Biotechnology, Yonsei University, Seodaemun-Gu Shinchon-Dong 134 120-749, Republic of Korea
2 Section of Immunobiology, Yale University, School of Medicine, New Haven, CT 06520, USA
3 Department of Pediatrics, Tokyo Medical and Dental University, School of Medicine, Tokyo 113-8519, Japan
Correspondence to: S.-K. Lee; E-mail: sjrlee{at}yonsei.ac.kr
The issue of whether three ITAMs in the TCR
chain can transmit qualitatively distinct signals or redundantly amplify TCR-mediated activation signals was extensively investigated using stable hCD8-
Jurkat transfectants which contain stepwise deletions of each ITAM or mutations of tyrosine residues in each ITAM of TCR
chain. The influence of mutations of each tyrosine residue on reduction of the amount and species of tyrosine phosphorylated proteins recruited to
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-
, 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
chain can transmit qualitatively differential intracellular signals upon TCR stimulation through distinctive regulation of recruitment of tyrosine phosphorylated proteins to
chain and activation of various MAPKs.
Keywords: apoptosis, cellular activation, signal transduction, T cell receptors
Transmitting editor: C. Terhorst
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