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J. Exp. Med., Volume 187, Number 7, April 6, 1998 1093-1101

T Cell Development in Mice Lacking All T Cell Receptor zeta  Family Members (zeta , eta , and Fcepsilon RIgamma )

By Elizabeth W. Shores,* Masao Ono,Dagger Tsutomo Kawabe,Dagger Connie L. Sommers,par Tom Tran,* Kin Lui,par Mark C. Udey,§ Jeffrey Ravetch,Dagger and Paul E. Lovepar

From the * Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the Dagger  Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York 10021; the § Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; and the par  Laboratory of Mammalian Genes & Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

The zeta  family includes zeta , eta , and Fcepsilon RIgamma (Fcgamma ). Dimers of the zeta  family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking zeta /eta chains, T cell development is impaired, yet low numbers of CD4+ and CD8+ T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a zeta  family dimer can promote T cell maturation, or that in the absence of zeta /eta , Fcgamma serves as a subunit in TCR complexes. To elucidate the role of zeta  family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only zeta /eta or Fcgamma . The data reveal that surface complexes that are expressed in the absence of zeta  family dimers are capable of transducing signals required for alpha /beta -T cell development. Strikingly, T cells generated in both zeta /eta -/- and zeta /eta -/--Fcgamma -/- mice exhibit a memory phenotype and elaborate interferon gamma . Finally, examination of different T cell populations reveals that zeta /eta and Fcgamma have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of zeta  family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations.


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