α/β T-cell antigen receptor gene and protein expression occurs at early stages of thymocyte differentiation

Alterations in gene expression that orchestrate eukaryotic cellular differentiation often require appropriate interactions between differentiating cells and a specialized microenvironment. During T-lymphocyte differentiation, immature thymocytes undergo a stringent intrathymic selection process that requires intimate contact with thymic stromal elements. Since this selection process generates T cells that are self-tolerant and recognize nominal antigen only within the context of self-major histocompatibility antigen complex molecules, it is possible that thymocyte/stromal cell interactions are mediated, in part, by antigen-specific receptors expressed on differentiating thymocytes. However, the developmental stage at which α/β antigen-specific receptors are expressed during T-cell maturation has been a matter of debate. To address this issue, we have studied α/β T-cell antigen receptor gene and protein expression on normal thymocyte subsets of AKR/J mice, as well as on a panel of AKR/J primary thymic lymphomas characterized for CD4 (L3T4) and CD8 (Lyt-2) differentiation antigen expression. The data unequivocally demonstrate that α/β heterodimers are expressed not only on phenotypically mature thymocytes but also on the majority of CD4⁺8⁺ double-positive cells that comprise the predominant nonmature thymocyte subset. Furthermore, a fraction of thymocytes in the CD4^-8^- double-negative compartment, known to contain progenitor cells, also expresses readily detectable cell-surface α/β receptors. Therefore, during the process of intrathymid selection, interactions between nonmature thymocytes and stromal cells via the antigen-receptor complex may play a pivotal role in T-cell differentiation and should be considered in formulating schemes for functional T-cell selection.