HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lacorazza, H. D. Articles by Nikolich-Zugich, J. Search for Related Content PubMed PubMed Citation Articles by Lacorazza, H. D. Articles by Nikolich-Zugich, J.

Exclusion and Inclusion of TCR Proteins during T Cell Development in TCR-Transgenic and Normal Mice¹

H. Daniel Lacorazza^2,* and Janko Nikolich-ugich^3,*,

^* Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; and Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006

Allelic exclusion of immune receptor genes (and molecules) is incompletely understood. With regard to TCR lineage T cells, exclusion at the tcr-b, but not tcr-a, locus seems to be strictly controlled at the locus rearrangement level. Consequently, while nearly all developing TCR thymocytes express a single TCR protein, many thymocytes rearrange and express two different TCR chains and, thus, display two TCRs on the cell surface. Of interest, the number of such dual TCR-expressing cells is appreciably lower among the mature T cells. To understand the details of TCR chain regulation at various stages of T cell development, we analyzed TCR expression in mice transgenic for two rearranged TCR. We discovered that in such TCR double-transgenic (TCRdTg) mice peripheral T cells were functionally monospecific. Molecularly, this monospecificity was due to TCR exclusion: one transgenic TCR protein was selectively down-regulated from the thymocyte and T cell surface. In searching for the mechanism(s) governing this selective TCR down-regulation, we present evidence for the role of protein tyrosine kinase signaling and coreceptor involvement. This mechanism may be operating in normal thymocytes.

This article has been cited by other articles:

				R. Casellas, Q. Zhang, N.-Y. Zheng, M. D. Mathias, K. Smith, and P. C. Wilson Ig{kappa} allelic inclusion is a consequence of receptor editing J. Exp. Med., January 22, 2007; 204(1): 153 - 160. [Abstract] [Full Text] [PDF]

				H. Tuovinen, J. T. Salminen, and T. P. Arstila Most human thymic and peripheral-blood CD4+CD25+ regulatory T cells express 2 T-cell receptors Blood, December 15, 2006; 108(13): 4063 - 4070. [Abstract] [Full Text] [PDF]

				Q. Ge, P. D. Holler, V. S. Mahajan, T. Nuygen, H. N. Eisen, and J. Chen Development of CD4+ T cells expressing a nominally MHC class I-restricted T cell receptor by two different mechanisms PNAS, February 7, 2006; 103(6): 1822 - 1827. [Abstract] [Full Text] [PDF]

				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]