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About the Authors:
Karen S. Hathcock
* E-mail: [email protected]
Affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Lila Farrington
Affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Irina Ivanova
Affiliation: Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
Ferenc Livak
Affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
Roza Selimyan
Affiliation: Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
Ranjan Sen
Affiliation: Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
Joy Williams
Affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Xuguang Tai
Affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
Richard J. Hodes
Affiliations Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
Introduction
In order to generate mature αβ T cells, developing thymocytes must negotiate developmental checkpoints that depend upon the rearrangement of TCR α and β genes. During conventional thymic development DN3 cells that express a surface pre-TCR consisting of a productively rearranged TCRβ chain, an invariant pre-TCRα chain, and CD3 components, successfully negotiate the “β checkpoint” and differentiate. Although circumstances have been described that allow the generation of DN4 cells in the absence of expressed TCRβ (and pre-TCR) or TCRγδ [1], [2] successful differentiation of the vast majority of DN4 thymocytes in adult mice requires pre-TCR signals to allow rescue from apoptosis, extensive proliferation, and development to CD4+CD8+ DP thymocytes [3], [4]. In addition pre-TCR signals also inhibit V-DJβ rearrangement on a second chromosome (allelic exclusion or β suppression) thereby assuring that each developing T cell expresses only a single TCRβ chain [5], [6]. We have studied TCRβ rearrangement and allelic exclusion and asked if these events absolutely require...