Regulation of LMP2 and TAP1 Genes by IRF-1 Explains the Paucity of CD8+ T Cells in IRF-1-/- Mice

Immunity. 1996 Oct;5(4):365-76. doi: 10.1016/s1074-7613(00)80262-9.

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