T cell receptor delta gene rearrangement and T early alpha (TEA) expression in immature alpha beta lineage thymocytes: implications for alpha beta/gamma delta lineage commitment.
Mature T cells comprise two mutually exclusive lineages expressing heterodimeric alpha beta or gamma delta antigen receptors. During development, beta, gamma, and delta genes rearrange before alpha, and mature gamma delta cells arise in the thymus prior to alpha beta cells. The mechanism underlying commitment of immature T cells to the alpha beta or gamma delta lineage is controversial. Since the delta locus is located within the alpha locus, rearrangement of alpha genes leads to deletion of delta. We have examined the rearrangement status of the delta locus immediately prior to alpha rearrangement. We find that many thymic precursors of alpha beta cells undergo VDJ delta rearrangements. Furthermore, the same cells frequently coexpress sterile T early alpha (TEA) transcripts originating 3' of C delta and 5' of the most upstream J alpha, thus implying that individual alpha beta lineage cells undergo sequential VDJ delta and VJ alpha rearrangements. Finally, VDJ delta rearrangements in immature alpha beta cells appear to be random, supporting models in which alpha beta lineage commitment is determined independently of the rearrangement status at the TCR delta locus.
Wilson
A
A
Ludwig Institute for Cancer Research, University of Lausanne, Epalinges, Switzerland.
de Villartay
J P
JP
MacDonald
H R
HR
D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C087435:Slc7a2 protein, mouse