T cell development and selection in the thymus

Abstract

T cell receptor (TCR) transgenic mice have been useful models to study the selection of lymphocytes during T cell development. They also have raised new questions with regard to allelic exclusion of T cell receptor genes and mechanisms determining the CD4/CD8 phenotype of mature T cells. Our data indicate that exclusion of beta and alpha TCR alleles occurs by different mechanisms: the expression of beta TCR genes as cell surface proteins in the absence of alpha, gamma or delta TCR chains apparently suppresses effectively further rearrangement of the beta TCR locus in spite of the presence of an active recombination machinery in these cells. In contrast an alpha TCR surface protein has little effect on further alpha TCR rearrangement which only ceases after positive selection of alpha beta T cells. This enables a developing T cell to test various alpha TCR chains with one beta TCR chain in the formation of a selectable receptor. Further data support the concept that different signals instruct developing T cells to either become CD4+8- helper or CD4-8+ killer cells: CD4+8+ cells with high levels of a class I MHC specific TCR were shown to result exclusively from positive selection and developed in vitro in the absence of selecting ligands in CD4-8+ but not CD4+8- T cells.