A Model for TCR Gene Segment Use1

The TCR -chain is assembled by somatic recombination of variable (V) and joining (J) gene segments at the CD4CD8 stage of development. In this study, we present the first analytical model for deletional rearrangement and show that it is consistent with almost all available data on VJ use in mice and humans. A key feature of the model is that both “local ” and “express service” models of rearrangement can be obtained by varying a single parameter that describes the number of gene segments accessible at a time. We find that the window is much larger for V segments than J segments, which reconciles seemingly conflicting data for the former. Implications for the properties of the repertoire as a whole and experiments that seek to probe them are discussed. Special considerations for allelic inclusion are treated in the Appendices. The Journal of Immunology, 2006, 177: 3857–3864. T o provide protection from pathogens, T lymphocytes mustreact to an enormous variety of foreign molecules. Thespecificity of a clone for Ag is determined by the TCRs on its surface, which are typically heterodimers of - and -chains. The diversity of the TCR repertoire derives in large part from the fact that both - and -chains are generated during intrathymic development by somatic recombination of gene segments encod-ing the constant and variable portions of these molecules. The latter include variable (V), diversity (D), and joining (J) gene seg-ments in the case of -chains and V and J gene segments in th