Involvement of CREB Binding Protein in Expression of Major Histocompatibility Complex Class II Genes via Interaction with the Class II Transactivator

ABSTRACT

The class II transactivator (CIITA) is a key regulatory factor that controls expression of the major histocompatibility complex (MHC) class II genes that are essential components for antigen presentation and thus regulation of the immune response. We show here that the adenovirus E1A protein interferes with the action of CIITA and inhibits both B-cell-specific and gamma interferon (IFN-γ)-induced expression of MHC class II promoters. Transfection studies provide evidence for the functional role of the CREB-binding protein (CBP) in IFN-γ and CIITA-mediated MHC class II promoter activation. We demonstrate that the N-terminally located transcription activation domain of CIITA physically interacts with both the N-terminal and the E1A-binding (C/H3) regions of CBP. These results suggest the involvement of a multisubunit complex, which contains the gene-specific coactivator CIITA and the versatile coactivator CBP, in MHC class II gene regulation, which may be responsible for both high-level expression and modulation by different signaling pathways.

ACKNOWLEDGMENTS

We thank T. Makatounakis for expert technical assistance and L. Kalogeraki for photographic work. We thank A. van der Eb for E1A plasmids. We are grateful to D. Thanos for plasmids, helpful discussions, and advice and to J. Talianidis and C. Mamalaki for critical reading.

This work was funded by the Greek Secretariat General for Research through institutional funds and by grant 236.234.603 of the European Union Program EPET II.