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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 {zeta} chain ITAMs and their tyrosine residues

Wook-Jin Chae1, Heung-Kyu Lee1, Jin-Hwan Han1, Sang-Won Vincent Kim1,2, Alfred L.M. Bothwell2, Tomohiro Morio3 and Sang-Kyou Lee1

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 {zeta} chain can transmit qualitatively distinct signals or redundantly amplify TCR-mediated activation signals was extensively investigated using stable hCD8-{zeta} Jurkat transfectants which contain stepwise deletions of each ITAM or mutations of tyrosine residues in each ITAM of TCR {zeta} chain. The influence of mutations of each tyrosine residue on reduction of the amount and species of tyrosine phosphorylated proteins recruited to {zeta} 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-{zeta}, 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 {zeta} chain can transmit qualitatively differential intracellular signals upon TCR stimulation through distinctive regulation of recruitment of tyrosine phosphorylated proteins to {zeta} chain and activation of various MAPKs.

Keywords: apoptosis, cellular activation, signal transduction, T cell receptors

Transmitting editor: C. Terhorst


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