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A T lymphocyte-specific transcription complex containing RUNX1 activates MHC class I expression
T Kevin Howcroft1, Jocelyn D Weissman, Anne Gegonne
1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|February 9, 2005
Summary
The T cell enhanceosome directly enhances Major Histocompatibility Complex (MHC) class I gene expression in T cells. This RUNX1-containing complex provides a molecular basis for high MHC class I levels in these immune cells.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Major Histocompatibility Complex (MHC) class I expression varies by tissue and hormone, with high levels in lymphoid cells like T and B cells.
- While the B cell enhanceosome explains high MHC class I in B cells, the mechanism in T cells remains unclear.
- T cell-specific genes are regulated by a T cell enhanceosome complex (RUNX1, CBFbeta, LEF1, Aly).
Purpose of the Study:
- To investigate the molecular basis for high constitutive MHC class I expression in T cells.
- To determine if the T cell enhanceosome regulates MHC class I gene expression.
Main Methods:
- Investigated the interaction of the T cell enhanceosome with MHC class I genes in vivo.
- Analyzed the synergistic effects of T cell enhanceosome and CIITA-mediated activation on MHC class I transcription.
Main Results:
- Demonstrated that the T cell enhanceosome directly enhances MHC class I gene expression in T cells.
- Showed a direct interaction between the RUNX1-containing complex and the MHC class I gene.
- Found that T cell enhanceosome activation is synergistic with CIITA and targets distinct elements.
Conclusions:
- The T cell enhanceosome provides a molecular mechanism for high MHC class I expression in T cells.
- This regulation is distinct from and synergistic with CIITA-mediated pathways.