T cell receptor gene recombination patterns and mechanisms: Cell death, rescue, and T cell production Journal Article
| Authors: | Petrie, H. T.; Livak, F.; Burtrum, D.; Mazel, S. |
| Article Title: | T cell receptor gene recombination patterns and mechanisms: Cell death, rescue, and T cell production |
| Abstract: | The antigen-specific receptors of T and B lymphocytes are generated by somatic recombination between noncontiguous gene segments encoding the variable portions of these molecules. The semirandom nature of this process, while desirable for the generation of diversity, has been thought to exact a high price in terms of sterile (out-of-frame) products. Historically, the majority of T lymphocytes generated in mammals were thought to be useless, either because they generated such sterile rearrangements or because the receptors generated did not appropriately recognize self-molecules (i.e., positive and negative selection). In the studies described here, we characterize the onset of T cell receptor (TCR) α and β chain gene rearrangements and quantitate their progression throughout T cell development. The results show that T cell production efficiency is enhanced through (a) rearrangement of TCR-β chain genes early during T cell development, with selective expansion of those cells possessing in-frame rearrangements; (b) deletion of sterile rearrangements at the TCR-α chain locus through ordered (proximal to distal) sequential recombination; and (c) modification of nonselectable α/β heterodimer specificities through generation and expression of new TCR-α chains. In addition, we demonstrate strict correlations between successful TCR-β gene rearrangement, the onset of TCR-α gene rearrangement, rapid cell division, and programmed cell death, which together serve to maintain cell turnover and homeostasis during T cell development. © 1995, Rockefeller University Press., All rights reserved. |
| Keywords: | controlled study; gene cluster; proto-oncogene proteins; nonhuman; animal cell; mouse; animal; mice; cell death; apoptosis; gene locus; cell differentiation; mice, inbred c57bl; mice, transgenic; t lymphocyte receptor beta chain; gene rearrangement; genetic recombination; recombination, genetic; t-lymphocyte subsets; homeostasis; proto-oncogene proteins c-bcl-2; t lymphocyte subpopulation; lymphocytopoiesis; receptors, antigen, t-cell, alpha-beta; t lymphocyte receptor alpha chain; gene rearrangement, t-lymphocyte; southern blotting; receptors, interleukin-2; t lymphocyte receptor gene; priority journal; article; gene rearrangement, alpha-chain t-cell antigen receptor; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; gene rearrangement, beta-chain t-cell antigen receptor |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 182 |
| Issue: | 1 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 1995-07-01 |
| Start Page: | 121 |
| End Page: | 127 |
| Language: | English |
| DOI: | 10.1084/jem.182.1.121 |
| PUBMED: | 7790812 |
| PROVIDER: | scopus |
| PMCID: | PMC2192092 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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