Negative and positive selection of immature thymocytes: timing and the role of the ligand for alpha beta T cell receptor.

Recent experiments show that CD4+8+ thymocytes represent the critical stage in T cell development at which the specificity of randomly generated ab T cell receptors is screened. These cells are deleted when the receptor binds to the MHC molecule plus specific peptide presented by bone marrow derived cells but are rescued from cell death and induced to mature if the receptor binds to the MHC molecule on thymic epithelium in the absence of the specific peptide. Different tolerogens delete CD4+8+ thymocytes earlier or later during their lifespan and negative selection can occur prior to positive selection. The specificity of the ab T cell receptor for either class I or class II thymic MHC molecules determines the CD4-8+ and CD4+8- phenotype of mature T cells.