Exclusion and inclusion of α and β T cell receptor alleles

Exclusion and inclusion of T cell receptor (TCR) genes were analyzed in αβ TCR transgenic mice. Both transgenes are expressed unusually early on the surface of CD4^-8^-, HSA⁺, IL-2R^- thymocytes. These progenitor cells give rise to progeny, which at the single-cell level contains endogenous α but not β TCR-RNA as well as protein, in addition to products encoded by the transgenes. Thus, the surface expression of an αβ TCR does not prevent further α TCR rearrangement in immature thymocytes that still transcribe RAG-1 and RAG-2 genes. Reduced levels of RAG-1 and RAG-2 RNA are detectable only in CD4⁺8⁺ TCR^high cells, which result from positive selection in the thymus. The results suggest that a developing T cell may try different αβ TCRs for binding to thymic MHC ligands, and that recombination at the α locus ceases only after positive selection.