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The Journal of Immunology, 2006, 177: 3857-3864.
Copyright © 2006 by The American Association of Immunologists, Inc.

A Model for TCR Gene Segment Use1

Aryeh Warmflash* and Aaron R. Dinner2,{dagger},{ddagger},§

* Department of Physics, {dagger} Department of Chemistry, {ddagger} Committee on Immunology, § Institute for Biophysical Dynamics, and James Franck Institute, University of Chicago, Chicago, IL 60637

The TCR {alpha}-chain is assembled by somatic recombination of variable (V) and joining (J) gene segments at the CD4+CD8+ 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 V{alpha}J{alpha} 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{alpha} segments than J{alpha} 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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 A.W. was supported by a National Science Foundation graduate research fellowship.

2 Address correspondence and reprint requests to Dr. Aaron R. Dinner, The University of Chicago, Gordon Center for Integrative Science, 929 E. 57th Street, Chicago, IL 60637. E-mail address: dinner{at}uchicago.edu

3 Abbreviation used in this paper: RAG, recombination activating gene.




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