T-CELL DEVELOPMENT IN MICE LACKING ALL T-CELL RECEPTOR-ZETA FAMILY MEMBERS (ZETA, ETA, AND FC-EPSILON-RI-GAMMA)

The zeta family includes zeta, eta, and Fc epsilon RI gamma (Fc gamma) . Dimers of the zeta family proteins function as signal transducing su bunits 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. Thi s finding suggests either that pre-TCR and TCR complexes lacking a zet a family dimer can promote T cell maturation, or that in the absence o f zeta/eta, Fc gamma serves as a subunit in TCR complexes. To elucidat e the role of zeta family dimers in T cell development, we generated m ice lacking expression of all of these proteins and compared their phe notype to mice lacking only zeta/eta or Fc gamma. The data reveal that surface complexes that are expressed in the absence of zeta family di mers are capable of transducing signals required for alpha/beta-T cell development. Strikingly, T cells generated in both zeta/eta(-/-) and zeta/eta(-/-)-Fc gamma(-/-) mice exhibit a memory phenotype and elabor ate interferon gamma. Finally, examination of different T cell populat ions reveals that zeta/eta and Fc gamma have distinct expression patte rns that correlate with their thymus dependency. A possible function f or the differential expression of zeta family proteins may be to impar t distinctive signaling properties to TCR complexes expressed on speci fic T cell populations.