# REGULATION OF MHC ANTIGEN EXPRESSION

> **NIH NIH R01** · STANFORD UNIVERSITY · 1987 · $167,605

## Abstract

Cell surface antigens encoded by the major histocompatibility
gene complex (MHC) function in the associative recognition of
foreign antigens by T lymphocytes, and the levels of their
expression affect both the induction and effector phases of
immune responses.  The expression of MHC antigens can be
modulated by several soluble mediators, perhaps the most
significant being the interferons (IFNs) which can be viewed as
being potent immunopotentiators.  Variability has been observed
in the MHC-inducing activities depending on the type of
interferon, the MHC gene, and the cell type.  Type I interferons
(alpha and beta, produced by virus-infected cells) stimulate
increases in the levels of class I MHC antigens in most cell types
but have no effect on class II antigen expression.  Type II
interferon (gamma, produced by activated T cells) stimulate
increases in class I expression and induce the expression of class II
antigens on some cell types, including macrophages and several
epithelial and endothelial cells.  The long range goal of this
research is to understand the physiological regulation of
expression of MHC antigens, both in normal individuals and in
instances where aberrant MHC antigen expression may be
associated with immunopathological conditions (such as graft
rejection and autoimmunity).  During this grant period our efforts
will focus on elucidating the molecular mechanisms by which the
interferons stimulate increased class I expression and induce class
II expression on various murine tissues.  Our previous studies on
the effects of IFN-gamma on the WEHI-3 macrophage cell line
suggest differences in the contribution of transcriptional and
post-transcriptional effects on IFN-gamma on expression of class
I and class II antigens and their associated chains, beta2-
microglobulin and the invariant chain.  We will quantitate the
contributions of increased transcription rates and mRNA
stabilization to the increased levels of MHC mRNAs in WEHI-3
cells and normal peritoneal macrophages.  These analyses will be
extended to the type I interferons and to other cell types (using
primary cell cultures) to assess interferon- and tissue-specific
variations in the mechanisms of stimulation of MHC expression.
Responsiveness of the various class I genes will be assessed by
using a set of gene-specific synthetic oligonucleotide probes, and
responses of individual class I and class II genes will be monitored
in mice of different H-2 haplotypes to investigate the possibility
that allele-specific differences in regulation of the levels of MHC
antigens could influence immune responsiveness and disease
susceptibility.  We will determine the mechanisms of action of
agents that modulate interferon responses:  prostaglandins and
glucocorticoids, which inhibit IFN-gamma-induced class II
expression, and tumor necrosis factor and lymphotoxin, which
synergize with IFN-gamma to increase the level of class II
induction.  Finally, we will investigate the mechanisms of
trans...

## Key facts

- **NIH application ID:** 3129416
- **Project number:** 2R01AI019964-04A1
- **Recipient organization:** STANFORD UNIVERSITY
- **SAM.gov UEI:** HJD6G4D6TJY5
- **Principal Investigator:** PATRICIA P JONES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $167,605
- **Award type:** 2
- **Project period:** 1983-09-30 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129416

## Citation

> US National Institutes of Health, RePORTER application 3129416, REGULATION OF MHC ANTIGEN EXPRESSION (2R01AI019964-04A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129416. Licensed CC0.

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