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TCR -Chain Repertoire in pT-Deficient Mice Is Diverse and Developmentally Regulated: Implications for Pre-TCR Functions and TCRA Gene Rearrangement¹

Stéphane Mancini^*, Serge M. Candéias^*, Hans Jorg Fehling, Harald von Boehmer, Evelyne Jouvin-Marche^* and Patrice N. Marche^2,*

^* 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; Basel Institute for Immunology, Basel, Switzerland; and Institut Necker, Institut National de la Santé et de la Recherche Médicale Unit 373, Paris, France

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 pT-deficient mice, a substantial number of ß⁺ thymocytes are still produced, in part because early TCR -chain expression can rescue immature thymocytes from cell death. In this study, the nature of these TCR -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 pT^-/- 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 pT 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 pT-derived signals for their differentiation.

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