In vitro and in vivo studies on the generation of the primary T-cell receptor repertoire.
The primary T-cell receptor repertoire is generated by somatic rearrangement of discontinuous gene segments. The shape of the combinatorial repertoire is stereotypical and, in part, evolutionarily conserved among mammals. Rearrangement is initiated by specific interactions between the recombinase and the recombination signals (RSs) that flank the gene segments. Conserved sequence variations in the RS, which modulate its interactions with the recombinase, appear to be a major factor in shaping the primary repertoire. In vitro, biochemical studies have revealed distinct steps in these complex recombinase-RS interactions that may determine the final frequency of gene segment rearrangement. These studies offer a plausible model to explain gene segment selection, but new, more physiological approaches will have to be developed to verify and refine the mechanism by which the recombinase targets the RS in its endogenous chromosomal context in vivo.
Livák
Ferenc
F
Department of Microbiology and Immunology, Graduate Program in Molecular and Cellular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. almassy@rocketmail.com
D000818:Animals; D001483:Base Sequence; D004249:DNA Damage / Q000502:physiology; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin / Q000276:immunology / Q000502:physiology; D019672:Genes, T-Cell Receptor; D006801:Humans; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology; D045567:VDJ Recombinases / Q000502:physiology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D045567:VDJ Recombinases