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Department of Molecular Biology, Princeton University, Princeton, NJ 08544; and
Fox Chase Cancer Center, Philadelphia, PA 19111
This series of papers addresses the effects of continuous Ag
receptor gene rearrangement in lymphocytes on allelic exclusion. The
previous paper discussed light chain gene rearrangement and receptor
editing in B cells, and showed that these processes are ordered on
three different levels. This order, combined with the constraints
imposed by a strong negative selection, was shown to lead to effective
allelic exclusion. In the present paper, we discuss rearrangement of
TCR genes. In the TCR 
-chain, allelic inclusion may be the rule
rather than the exception. Several previous models, which attempted to
explain experimental observations, such as the fractions of cells
containing two productive TCR rearrangements, did not sufficiently
account for TCR gene organization, which limits secondary
rearrangement, and for the effects of subsequent thymic selection. We
present here a detailed, comprehensive computer simulation of TCR gene
rearrangement, incorporating the interaction of this process with other
aspects of lymphocyte development, including cell division, selection,
cell death, and maturation. Our model shows how the observed fraction
of T cells containing productive TCR rearrangements on both alleles
can be explained by the parameters of thymic selection imposed over a
random rearrangement process.
This article has been cited by other articles:
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  C. van den Dool and R. J. de Boer The Effects of Age, Thymectomy, and HIV Infection on {alpha} and beta TCR Excision Circles in Naive T Cells J. Immunol., October 1, 2006; 177(7): 4391 - 4401. [Abstract] [Full Text] [PDF]
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A. Warmflash, M. Weigert, and A. R. Dinner Control of Genotypic Allelic Inclusion through TCR Surface Expression J. Immunol., November 15, 2005; 175(10): 6412 - 6419. [Abstract] [Full Text] [PDF]
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M. S. Zand, B. J. Briggs, A. Bose, and T. Vo Discrete Event Modeling of CD4+ Memory T Cell Generation J. Immunol., September 15, 2004; 173(6): 3763 - 3772. [Abstract] [Full Text] [PDF]
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R. Mehr, H. Edelman, D. Sehgal, and R. Mage Analysis of Mutational Lineage Trees from Sites of Primary and Secondary Ig Gene Diversification in Rabbits and Chickens J. Immunol., April 15, 2004; 172(8): 4790 - 4796. [Abstract] [Full Text] [PDF]
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K. Laky, J. M. Lewis, R. E. Tigelaar, and L. Puddington Distinct Requirements for IL-7 in Development of TCR{gamma}{delta} Cells During Fetal and Adult Life J. Immunol., April 15, 2003; 170(8): 4087 - 4094. [Abstract] [Full Text] [PDF]
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G. Kalmanovich and R. Mehr Models for Antigen Receptor Gene Rearrangement. III. Heavy and Light Chain Allelic Exclusion J. Immunol., January 1, 2003; 170(1): 182 - 193. [Abstract] [Full Text] [PDF]
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