The Tcrbeta loci: Mechanisms controlling rearrangement and allelic exclusion
Abstract
Assembly of variable (V), diversity (D), and joining (J) segments to form a T cell receptor β (Tcr β) exon has multiples levels of control. Despite years of investigation, mechanisms directing three main phases of recombination are unclear: one, the order of Dβ-to-Jβ rearrangement followed by Vβ-to-DJβ rearrangement; two, Vβ segment choice and limitations on recombination; and three, the restriction of cell-surface expression to one Tcr β exon. In this work, I have assessed mechanisms for each of these phases using mouse models containing pre-assembled DJβ complexes, functional Tcr β exons, and a V(D)J recombinase reporter. I have found ordered rearrangement is controlled in part by restricting Vβ recombinase access during development and this two-step process influences TCRβ chain selection and the peripheral Vβ repertoire. The regulation of Vβ-to-DJβ rearrangements is not due to limiting recombinase access, as I have found Vβ14 accessibility to be bi-allelic and abundant. In addition, introduction of a pre-assembled Tcr β exon reduced endogenous Vβ-to-DJβ recombination, as expected, and Vβ-to-reporter recombination; moreover these experiments revealed the existence of mechanisms separate from recombination that can enforce Tcr β allelic exclusion.
Subject Area
Immunology
Recommended Citation
Andrea Christine Carpenter,
"The Tcrbeta loci: Mechanisms controlling rearrangement and allelic exclusion"
(January 1, 2009).
Dissertations available from ProQuest.
Paper AAI3363262.
http://repository.upenn.edu/dissertations/AAI3363262
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