ALPHA-BETA LINEAGE-COMMITTED THYMOCYTES CAN BE RESCUED BY THE GAMMA-DELTA T-CELL RECEPTOR (TCR) IN THE ABSENCE OF TCR BETA-CHAIN

Commitment of the alpha beta and gamma delta T cell lineages within th e thymus has been studied in T cell receptor (TCR)-transgenic and TCR mutant murine strains. TCR gamma delta-transgenic or TCR beta knockout mice, both of which are unable to generate TCR alpha beta-positive T cells, develop phenotypically alpha beta-like thymocytes in significan t proportions. We provide evidence that in the absence of functional T CR beta protein, the gamma delta TCR can promote the development of al pha beta-like thymocytes, which, however, do not expand significantly and do not mature into gamma beta T cells. These results show that com mitment to the alpha beta lineage can be determined independently of t he isotype of the TCR, and suggest that alpha beta versus gamma delta T cell lineage commitment is principally regulated by mechanisms disti nct from TCR-mediated selection. To accommodate our data and those rep orted previously on the effect of TCR gamma and delta gene rearrangeme nts on alpha beta T cell development, we propose a model in which line age commitment occurs independently of TCR gene rearrangement.