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Publication : TCR alpha-chain repertoire in pTalpha-deficient mice is diverse and developmentally regulated: implications for pre-TCR functions and TCRA gene rearrangement.

First Author  Mancini S Year  1999
Journal  J Immunol Volume  163
Issue  11 Pages  6053-9
PubMed ID  10570293 Mgi Jnum  J:58653
Mgi Id  MGI:1349315 Doi  10.4049/jimmunol.163.11.6053
Citation  Mancini S, et al. (1999) TCR alpha-chain repertoire in pTalpha-deficient mice is diverse and developmentally regulated: implications for pre-TCR functions and TCRA gene rearrangement. J Immunol 163(11):6053-9
abstractText  Pre-TCR expression on developing thymocytes allows cells with productive TCRB gene rearrangements to further differentiate. In wild-type mice, most TCRA gene rearrangements are initiated after pre-TCR expression. However, in pTalpha-deficient mice, a substantial number of alphabeta+ thymocytes are still produced, in part because early TCR alpha-chain expression can rescue immature thymocytes from cell death. In this study, the nature of these TCR alpha-chains, produced and expressed in the absence of pre-TCR expression, have been analyzed. We show, by FACS analysis and sequencing of rearranged transcripts, that the TCRA repertoire is diverse in pTalpha-/- mice and that the developmental regulation of AJ segment use is maintained, yet slightly delayed around birth when compared with wild-type mice. We also found that T cell differentiation is more affected by pTalpha inactivation during late gestation than later in life. These data suggest that the pre-TCR is not functionally required for the initiation and regulation of TCRA gene rearrangement and that fetal thymocytes are more dependent than adult cells on pTalpha-derived signals for their differentiation.
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