TCR alpha-chain repertoire in pTalpha-deficient mice is diverse and developmentally regulated: implications for pre-TCR functions and TCRA gene rearrangement.
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.
Mancini
S
S
Laboratoire d'Immunochimie, Commissariat à l'Energie Atomique-Grenoble, Département de Biologie Moléculaire et Structurale, Institut National de la Santé et de la Recherche Médicale Unit 238, Université Joseph Fourier, Grenoble, France.
Candéias
S M
SM
Fehling
H J
HJ
von Boehmer
H
H
Jouvin-Marche
E
E
Marche
P N
PN
D000818:Animals; D002454:Cell Differentiation; D003001:Cloning, Molecular; D005434:Flow Cytometry; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000254:growth & development*
D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha