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Publication : Cutting Edge: CD3 ITAM Diversity Is Required for Optimal TCR Signaling and Thymocyte Development.

First Author  Bettini ML Year  2017
Journal  J Immunol Volume  199
Issue  5 Pages  1555-1560
PubMed ID  28733484 Mgi Jnum  J:251324
Mgi Id  MGI:6099905 Doi  10.4049/jimmunol.1700069
Citation  Bettini ML, et al. (2017) Cutting Edge: CD3 ITAM Diversity Is Required for Optimal TCR Signaling and Thymocyte Development. J Immunol 199(5):1555-1560
abstractText  For the alphabeta or gammadeltaTCR chains to integrate extracellular stimuli into the appropriate intracellular cellular response, they must use the 10 ITAMs found within the CD3 subunits (CD3gammaepsilon, CD3deltaepsilon, and zetazeta) of the TCR signaling complex. However, it remains unclear whether each specific ITAM sequence of the individual subunit (gammaepsilondeltazeta) is required for thymocyte development or whether any particular CD3 ITAM motif is sufficient. In this article, we show that mice utilizing a single ITAM sequence (gamma, epsilon, delta, zetaa, zetab, or zetac) at each of the 10 ITAM locations exhibit a substantial reduction in thymic cellularity and limited CD4(-)CD8(-) (double-negative) to CD4(+)CD8(+) (double-positive) maturation because of low TCR expression and signaling. Together, the data suggest that ITAM sequence diversity is required for optimal TCR signal transduction and subsequent T cell maturation.
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