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Allelic Exclusion at the TCR Locus and Commitment to Lineage: Different Modalities Apply to Distinct Human Subsets¹

Institut National de la Santé et de la Recherche Médicale Unité 463, Institut de Biologie, Nantes, France

Expression of a -chain, as a pre-TCR, in T cell precursors prevents further rearrangements on the alternate allele through a strict allelic exclusion process and enables precursors to undergo differentiation. However, whether allelic exclusion applies to the TCR locus is unknown and the role of the TCR in lineage commitment is still unclear. Through the analysis of the rearrangement status of the TCR, , and loci in human T cell clones, expressing either the TCR V1 or V2 variable regions, we show that the rate of partial rearrangements at the locus is consistent with an allelic exclusion process. The overrepresentation of clones with two functional TCR chains indicates that a TCR selection process is required for the commitment of T cell precursors to the lineage. Finally, while complete TCR rearrangements were observed in several V2 T cell clones, these were seldom found in V1 cells. This suggests a competitive / lineage commitment in the former subset and a precommitment to the lineage in the latter. We propose that these distinct behaviors are related to the developmental stage at which rearrangements occur, as suggested by the patterns of accessibility to recombination sites that characterize the V1 and V2 subsets.

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