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

Abstract

The thymus is the major site for T-cell receptor (TCR) gene rearrangement and T-cell maturation^1,2. 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, TCRα and TCRβ, expressed in non-covalent association with an invariant complex of proteins, CD3 (T3)^3–6. Recently, a novel TCR/CD3 complex, that includes the product of the TCRγ gene, has been identified on a subset of both peripheral cells and thymocytes^7–9. 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 TCRγ-specific RNA, low levels of TCRβ-specific RNA and no detectable TCRα-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.