Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors

The T-cell repertoire is elaborated by a still poorly understood process during which precursor cells arising in the bone marrow seed the thymus to provide a starting point for intrathymic differentiation and selection. The products of the process are cells which express antigen receptors composed of either α/β or γ/δ heterodimers in association with CD3 (refs 1-3). The finding that the appearance of T-cell antigen receptor γ- and δ-gene rearrangements and transcripts precedes those of full-length β- and α-transcripts during ontogeny indicates that the process is ordered, a conclusion supported by the fact that the appearance of thymocytes expressing CD3-associated γ/δ heterodimers precedes the appearance of those bearing α/β heterodimers. The recent demonstrations that within the γ- and δ-loci there is ordered and sometimes transient rearrangement and expression of specific Vδ and Vγ gene segments during ontogeny raised the possibility that qualitative changes in the capacity of the differentiative process to generate components of the T-cell armamentarium might occur. We have produced a monoclonal antibody that detects an epitope of the Vγ3 gene product, a gene segment expressed only in the early fetal thymus. In this report we demonstrate that cells expressing Vγ3 are present transiently at the earliest stages of thymocyte development, preceding the appearance of cells bearing other γ/δ or α/β receptors. In the adult mouse, Vγ3 expression appears to be limited to Thy-1⁺ cells in the epidermis. These results suggest a profound programming and staging in elaboration of the components of the T-cell system during the early stages of thymocyte development in the embryo.