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T Cell Development in Mice Lacking All T Cell Receptor Family Members (, , and FcRI)

Elizabeth W. Shores^*, Masao Ono, Tsutomo Kawabe, Connie L. Sommers^||, Tom Tran^*, Kin Lui^||, Mark C. Udey, Jeffrey Ravetch, and Paul E. Love^||

From the ^* Division of Hematologic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892; the 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 ^|| Laboratory of Mammalian Genes & Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

The family includes , , and FcRI (Fc). Dimers of the 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 / 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 family dimer can promote T cell maturation, or that in the absence of /, Fc serves as a subunit in TCR complexes. To elucidate the role of family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only / or Fc. The data reveal that surface complexes that are expressed in the absence of family dimers are capable of transducing signals required for /β–T cell development. Strikingly, T cells generated in both /^–/– and /^–/––Fc^–/– mice exhibit a memory phenotype and elaborate interferon . Finally, examination of different T cell populations reveals that / and Fc have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations.

¹ Abbreviations used in this paper: DETC, dendritic epidermal T cell; DN, double negative; DP, double positive; Fc, FcRI; FCM, flow cytometric analysis; i-IEL, intestinal-intraepithelial lymphocytes; ITAM, immune-recptor tyrosine-based activation motif; SP, single positive.

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