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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3804-3808
Synergistic induction of HLA class I expression by RelA and CIITA
John Girdlestone
From the Anatomy Department, MRC Centre for Immune Regulation, The
Medical School, University of Birmingham, Birmingham, UK.
The major histocompatibility complex (MHC) class I genes are induced
synergistically by interferons (IFN) and tumor necrosis factor (TNF) , a response thought to involve the cooperative action of Rel/NF-kB and
interferon regulatory factor (IRF) transcription factors. The
IFN- -inducible class II transcriptional activator (CIITA) has
recently been shown to transactivate MHC class I as well as class II
genes, and this investigation shows that CIITA synergizes strongly with
RelA to stimulate HLA class I expression. The functional interaction of
CIITA and RelA requires both promoter elements and the upstream Rel
binding site and is not seen with a class II reporter. The promoter
elements necessary for CIITA action are also required for induction by
IFN- . HLA-A and HLA-B loci respond differentially to IFNs, and we
identify locus-specific differences in critical promoter elements in
addition to known polymorphisms in the Rel and IRF binding sites. The
HLA-A promoter is transactivated relatively poorly by CIITA and does
not interact detectably with CREB proteins implicated in
CIITA recruitment, but the synergism with RelA can compensate for this
weakness. The present findings illustrate that multiple transcription
factors cooperate to regulate class I expression and that their
relative importance differs according to the locus and cell type examined.
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Locus-specific regulation of HLA-A and HLA-B expression is not determined by nucleotide variation in the X2 box promoter element
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