The cellular and molecular mechanism of CD4/CD8 lineage commitment.
A unique feature of alpha beta T-cell development is the central role played by clonally distributed T-cell receptors (TCR), which are encoded by somatically rearranged gene segments that produce a diverse, non-germline encoded set of receptors. Fate determination in individual T-cells is mediated by ligand-receptor signals that arise from unprogrammed genetic interactions, under conditions in which the relevant ligand concentration and the receptor affinity are not evolutionarily controlled. A precursor T-cell with a TCR that either fails to demonstrate appreciable self-reactivity or binds with high affinity to reasonably abundant self-peptide major histocompatibility complex (MHC)-ligands will undergo apoptosis. In contrast, a precursor T-cell that shows lower affinity to moderately abundant ligands will receive suitable signals for survival and maturation. Recently, we have developed a rapid in vitro two-step organ culture system that permits homogeneous populations of non-transformed precursor T-cells to undergo selective commitment to the CD4 or CD8 lineage. Using this model, we have shown that the choice of positively selected ab T-cells between the CD4 helper and CD8 cytotoxic lineages is regulated by the TCR signaling duration in response to self-peptides bound to the MHC.
Yasutomo
Koji
K
Department of Parasitology and Immunology, University of Tokushima School of Medicine, Kuramoto-cho, Tokushima 770-8503, Japan.
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology
D016693:Receptors, Antigen, T-Cell, alpha-beta