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T-cell development

Committing to the CD4 lineage

Nature Reviews Immunology volume 5, page 264 (2005)Cite this article

Positive selection of a thymocyte occurs if its T-cell receptor (TCR) interacts with a self-peptide–MHC complex. The CD4/CD8 lineage choice occurs concomitantly with this, and it correlates with TCR engagement of self-peptide–MHC class II or class I, respectively. Previous studies of mice with a spontaneous recessive mutation, the helper deficient (HD) mutation, identified a locus that is required for CD4 lineage commitment, because in these mice, MHC-class-II-restricted thymocytes are redirected to the CD8 lineage. So, He et al. set out to characterize the molecular defects in HD mice. Initial studies showed that the redirection of MHC-class-II-restricted thymocytes to the CD8 lineage was not the result of either a defect in CD4 expression or inappropriate upregulation of CD8 expression. Similarly, no defects in signalling downstream of the TCR were detected, indicating that the HD mutation affects only T-cell lineage commitment.

Genetic mapping and a bacterial-artificial-chromosome complementation approach were used to identify Th-pok as the candidate HD gene. Consistent with this, in HD mice, cDNA encoding Th-POK was shown to have a single nucleotide substitution that resulted in an amino-acid substitution at a position predicted to mediate DNA binding.

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ORIGINAL RESEARCH PAPER

  1. He, X. et al. The zinc finger transcription factor Th-POK regulates CD4 versus CD8 T-cell lineage commitment. Nature 433, 826–833 (2005).

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Authors
  1. Karen Honey
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Honey, K. Committing to the CD4 lineage. Nat Rev Immunol 5, 264 (2005). https://doi.org/10.1038/nri1597

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