International Immunology, Vol 10, 1203-1210, Copyright © 1998 by Oxford University Press
Y Kametani, H Goto, A Kobori, T Sato, K Ando, K Hozumi, T Nishimura, T Saito, T Yamamoto and S Habu
Antigen stimulation via TCR in mature T cells provides rapid induction of
tyrosine phosphorylation of intracellular substrates including ZAP- 70. To
study the potential involvement of tyrosine phosphorylation in CD4+CD8+
[double-positive (DP)] thymocytes in the positive selection process in
vivo, we isolated and analyzed them in the presence of phosphatase
inhibitor. DP thymocytes were obtained from TCR transgenic mice (TCR-Tg)
expressing MHC class I- or class II-restricted TCR in selecting and
non-selecting MHC backgrounds respectively. The phosphorylation of ZAP-70
in DP thymocytes of class I-restricted TCR-Tg was significantly higher in
the positively selecting background than in the non-selecting one. However,
such a phosphorylation difference between selecting and non-selecting
TCR-Tg was found to be considerably less in class II-restricted TCR-Tg. A
similar bias for ZAP-70 phosphorylation was also observed on selecting DP
thymocytes when I- A(beta) deficient- and beta2-microglobulin-deficient
mice were compared. These ex vivo studies suggest that TCR-mediated
signaling on DP thymocytes induces ZAP-70 phosphorylation under a different
manner of engagement of TCR to class I and class II molecules in the
positive selection process.
ARTICLES
Ex vivo evidence for asymmetric tyrosine phosphorylation of ZAP-70 on double-positive thymocytes in the positive selection process
Department of Immunology, Tokai University School of Medicine, Kanagawa, Japan.
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