Positive selection as a developmental progression initiated by alpha beta TCR signals that fix TCR specificity prior to lineage commitment

During positive selection, immature thymocytes commit to either the CD4(+) or CD8(+) T cell lineage ("commitment") and convert from short-lived thymoc ytes into long-lived T cells ("rescue"). By formal precursor-progeny analys is, we now identify what is likely to be the initial positive selection ste p signaled by alpha beta TCR, which we have termed "induction". During indu ction, RAG mRNA expression is downregulated, but lineage commitment does no t occur. Rather, lineage commitment (which depends upon the MHC class speci ficity of the alpha beta TCR) only occurs after downregulation of RAG expre ssion and the consequent fixation of alpha beta TCR specificity. We propose that positive selection can be viewed as a sequence of increasingly select ive developmental steps (induction-->commitment-->rescue) that are signaled by alpha beta TCR engagements of intrathymic ligands.