Characterization of murine thymocytes with CD3-associated T-cell receptor structures

Abstract

The thymus is the major site for T-cell receptor (TCR) gene rearrangement and T-cell maturation. The specific antigen recognition structure (TCR) on murine T cells has been shown to be dependent on a polymorphic set of disulphide-linked heterodimers, containing two integral membrane glycoprotein chains, TCR alpha and TCR beta, expressed in non-covalent association with an invariant complex of proteins, CD3 (T3). Recently, a novel TCR/CD3 complex, that includes the product of the TCR gamma gene, has been identified on a subset of both peripheral cells and thymocytes. Here we examine the expression of TCR/CD3 complexes in fetal ontogeny and in the adult thymus. The results demonstrate that CD3+4-8-(T3+,L3T4-,Lyt2-)cells are detected in day-15 fetal thymi, throughout fetal development and in adult thymus. In situ hybridization studies indicate that these early CD3+ cells express high levels of TCR gamma-specific RNA, low levels of TCR beta-specific RNA and no detectable TCR alpha-specific RNA. Day-16 CD3+,4-,8- fetal thymocytes can be activated to proliferate and demonstrate cytolytic activity when cultured in the presence of anti-CD3 monoclonal antibodies and interleukin-2 (IL-2). These results suggest that CD3-bearing cells, present early in thymic ontogeny, express a functional TCR and may, therefore, be important in repertoire development.