Ontogeny of the T-cell antigen receptor within the thymus

Abstract

The expression of T-cell antigen receptors during T-cell ontogeny is an important issue that bears directly on such questions as where T-cell tolerance is acquired, at what stage T cells become susceptible to repertoire selection, and why most thymocytes die within the thymus. The thymus rudiment is colonized during days 11 and 12 of gestation, but it is not until day 19 that significant numbers of functional thymocytes are present. Although much is known about the ontogeny of function- and specificity-associated surface molecules such as Ly2 and MT4 (the murine equivalent of human T4) during this period, the ontogeny of the T-cell antigen receptors remains obscure. We have now addressed this question on three levels: DNA rearrangement, messenger RNA transcription and expression of cell-surface receptor-like proteins. Our results suggest that T-cell receptors are first expressed within the thymus around day 17 of gestation, independently of and probably before the expression of Ly2 and MT4. Furthermore, these data suggest that all major adult thymocyte subpopulations, including the small cortical cells, most of which die within the thymus, express receptors.