STOCHASTIC COMPONENT TO DEVELOPMENT OF CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-SPECIFIC T-CELLS

The mechanism by which an initially uncommitted cell chooses between a lternative fates is a central issue in developmental biology. In the m ammalian thymus, CD4 helper T cells and CD8 cytotoxic T cells arise fr om a common precursor that expresses both CD4 and CD8. The choke betwe en the CD4 and CD8 lineage is linked to the specificity of the T-cell antigen receptor expressed by a thymocyte, but whether lineage commitm ent is stochastic or instructed has not been definitively resolved. We present evidence that expression of a constitutive CD8 transgene duri ng thymic selection permits development of mature CD4 cells bearing th e class I-restricted F5 T-cell antigen receptor. These results suggest that there is a stochastic component to the development of class I ma jor histocompatibility complex-restricted T cells.