Abstract
The TAP1 and LMP2 genes are central for class I MHC function and share a common promoter. Here, we analyze the molecular mechanism of IFN gamma up-regulation of TAP1 and LMP2. In vivo footprinting indicates IFN gamma up-regulates protein-DNA contacts at an IRF-E that is essential for the up-regulation of TAP1 and LMP2 by IFN gamma. Gel shift analysis indicates that this site binds IRF-1. The expression of TAP1 and LMP2 are both greatly reduced in IRF-1-deficient mice. Surface class I MHC as well as CD8+ T cells are reduced in IRF-1-/- mice. The role of IRF-1 in the regulation of TAP1 and LMP2 suggests a mechanism for the antiviral properties of IRF-1 and the unexpected deficiency of CD8+ T cells observed in IRF-1-/- mice.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP-Binding Cassette Transporters / genetics*
-
Animals
-
CD8-Positive T-Lymphocytes / cytology*
-
Cell Differentiation
-
Cysteine Endopeptidases*
-
DNA Footprinting
-
DNA-Binding Proteins / physiology*
-
Gene Expression Regulation, Developmental
-
Genes, MHC Class I
-
Interferon Regulatory Factor-1
-
Interferon-gamma / physiology*
-
Mice
-
Mice, Transgenic
-
Phosphoproteins / physiology*
-
Promoter Regions, Genetic
-
Proteins / genetics*
-
RNA, Messenger / genetics
-
Up-Regulation
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP-Binding Cassette Transporters
-
DNA-Binding Proteins
-
Interferon Regulatory Factor-1
-
Irf1 protein, mouse
-
Phosphoproteins
-
Proteins
-
RNA, Messenger
-
TAP1 protein, human
-
Tap1 protein, mouse
-
LMP-2 protein
-
Interferon-gamma
-
Cysteine Endopeptidases