The Journal of Experimental Medicine
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Published online 18 September 2000.
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© The Rockefeller University Press, 0022-1007/2000/9/913/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 6, September 18, 2000 913-920


Brief Definitive Reports

Function of CD3{epsilon}-mediated Signals in T Cell Development

Connie L. Sommersa, Jan B. Dejarnettea, Kun Huanga, Jan Leeb, Dalal El-Khourya, Elizabeth W. Shoresb, and Paul E. Lovea
a Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892
b Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Correspondence to: Paul E. Love, Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892. Tel:301-402-4946 Fax:301-480-6302

The T cell antigen receptor (TCR) and pre-TCR complexes are composed of multiple signal-transducing subunits (CD3{gamma}, CD3{delta}, CD3{epsilon}, and {zeta}) that each contain one or more copies of a semiconserved functional motif, the immunoreceptor tyrosine-based activation motif (ITAM). Although biochemical studies indicate that individual TCR-ITAMs may bind selectively or with different affinity to various effector molecules, data from other experiments suggest that at least some ITAMs are functionally equivalent. In this study, we examined the role of CD3{epsilon} ITAM-mediated signals in T cell development by genetically reconstituting CD3{epsilon}-deficient mice with transgenes encoding either wild-type or ITAM-mutant (signaling defective) forms of the protein. The results demonstrate that signals transduced by CD3{epsilon} are not specifically required for T cell maturation but instead contribute quantitatively to TCR signaling in a manner similar to that previously observed for {zeta} chain. Unexpectedly, analysis of TCR-transgenic/CD3{epsilon}-mutant mice reveals a potential role for CD3{epsilon} signals in T cell survival.

Key Words: TCR, CD3epsilon, development, mice, cell survival


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