The Journal of immunology (1950), 2001-05, Vol.166 (10), p.6181-6187
2001
Details
- Autor(en) / Beteiligte
- Titel
- Positive and Negative Roles of the Trans-Acting T Cell Factor-1 for the Acquisition of Distinct Ly-49 MHC Class I Receptors by NK Cells
- Ist Teil von
- The Journal of immunology (1950), 2001-05, Vol.166 (10), p.6181-6187
- Ort / Verlag
- United States: Am Assoc Immnol
- Erscheinungsjahr
- 2001
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Members of the Ly-49 gene family code for class I MHC-specific receptors that regulate NK cell function. Due to a combinatorial distribution of Ly-49 receptors, NK cells display considerable clonal heterogeneity. The acquisition of one Ly-49 receptor, Ly-49A is strictly dependent on the transcriptional trans-acting factor T cell-specific factor-1 (TCF-1). Indeed, TCF-1 binds to two sites in the Ly-49a promoter and regulates its activity, suggesting that the Ly-49a gene is a direct TCF-1 target. TCF-1 deficiency resulted in the altered usage of additional Ly-49 receptors. We show in this study, using TCF-1 beta(2)-microglobulin double-deficient mice, that these repertoire alterations are not due to Ly-49/MHC class I interactions. Our findings rather suggest a TCF-1-dependent, cell autonomous effect on the acquisition of multiple Ly-49 receptors. Besides reduced receptor usage (Ly-49A and D), we also observed no effect (Ly-49C) and significantly expanded (Ly-49G and I) receptor usage in the absence of TCF-1. These effects did not in all cases correlate with the presence of TCF binding sites in the respective proximal promoter. Therefore, besides TCF-1 binding to the proximal promoter, Ly-49 acquisition may also be regulated by TCF-1 binding to more distant cis-acting elements and/or by regulating the expression of additional trans-acting factors. Consistent with the observed differential, positive or negative role of TCF-1 for Ly-49 receptor acquisition, reporter gene assays revealed the presence of an inducing as well as a repressing TCF site in certain proximal Ly-49 promoters. These findings reveal an important role of TCF-1 for the formation of the NK cell receptor repertoire.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1767eISSN: 1550-6606DOI: 10.4049/jimmunol.166.10.6181Titel-ID: cdi_proquest_miscellaneous_70837382
- Format
- –
- Schlagworte
- 5' Untranslated Regions - analysis, 5' Untranslated Regions - isolation & purification, Animals, Antigens, Ly, Base Sequence, Binding Sites - genetics, Binding Sites - immunology, Carrier Proteins - genetics, Carrier Proteins - metabolism, Cells, Cultured, DNA-Binding Proteins - deficiency, DNA-Binding Proteins - genetics, DNA-Binding Proteins - physiology, Hepatocyte Nuclear Factor 1-alpha, Histocompatibility Antigens Class I - genetics, Histocompatibility Antigens Class I - metabolism, Killer Cells, Natural - metabolism, Lectins, C-Type, Ly-49 antigen, Lymphoid Enhancer-Binding Factor 1, Membrane Glycoproteins - genetics, Membrane Glycoproteins - metabolism, Membrane Proteins - genetics, Membrane Proteins - metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Molecular Sequence Data, Peptide Fragments - genetics, Peptide Fragments - metabolism, Peptide Fragments - physiology, Promoter Regions, Genetic - immunology, Receptors, Immunologic - genetics, Receptors, Immunologic - metabolism, Receptors, NK Cell Lectin-Like, T Cell Transcription Factor 1, TCF-1 protein, Transcription Factors - deficiency, Transcription Factors - genetics, Transcription Factors - physiology, Tumor Cells, Cultured