EXCLUSION AND INCLUSION OF ALPHA-T-CELL AND BETA-T-CELL RECEPTOR ALLELES

Exclusion and inclusion of T cell receptor (TCR) genes were analyzed in alpha-beta-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-alpha but not beta-TCR-RNA as well as protein, in addition to products encoded by the transgenes. Thus, the surface expression of an alpha-beta-TCR does not prevent further alpha-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 alpha-beta-TCRs for binding to thymic MHC ligands, and that recombination at the alpha-locus ceases only after positive selection.