# CELLULAR IMMUNITY TO ENDOGENOUS AKR LEUKEMIA VIRUSES

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1992 · $230,667

## Abstract

DESCRIPTION:  (Adapted from the applicant's abstract) The long range goals
of this project are to define the molecular specificity of cytolytic T
lymphocytes (CTL) raised against esotropic murine leukemia viruses (MuLV);
to determine whether it is possible to generate CTL that are specific for
recombinant mink cell focus-inducing (MCF) MuLV and if so, to characterize
these MCF MuLV directed CTL and define their molecular specificity; and to
further determine the mechanism underlying the inability of the K-k class I
major histocompatibility complex (MHC) gene of the MuLV-induced tumor AKR
SL3 to show up-regulated expression in response to treatment with
interferon gamma (IFN-gamma).  The latter phenomenon of a differential
resistance of MHC genes of a tumor to IFN-gamma up-regulation (because the
D-k class I gene of AKR SL3 demonstrates normal responsiveness to
IFN-gamma) may be indicative of a tumor escape mechanism from the H-2K
restricted CTL responses that have been demonstrated to AKR/Gross
MuLV-induced tumors.  Thus, AKR SL3, which shows a low level of
constitutive expression of the class I MHC K-k gene product that is
required for CTL recognition and whose K-k gene additionally is IFN-gamma
noninducible, may have become established via an immunoselection driven by
anti-retroviral CTL.  The studies proposed to define the molecular
specificity of anti-retroviral CTL for MuLV-encoded determinants also have
relevance to the understanding of leukemogenesis.  Thus, in the AKR/Gross
MuLV leukemogenesis model certain mouse strains such as AKR, which have a
high incidence of spontaneous leukemia, express endogenous esotropic MuLV
very early in life neonatally, if not before.  This early expression of
esotropic MuLV is necessary for subsequent leukemogenesis which begins at
about six months of age just following the generation of recombinant
retroviruses, including most notably the MCF MuLV that are generally
considered to be the proximal transforming agent.  Because it is widely
thought that CTL are particularly effective against virus infected cells
and tumor cells, it is important to understand to which MuLV CTL can be
directed and their molecular specificity.

## Key facts

- **NIH application ID:** 3174451
- **Project number:** 5R01CA036860-10
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** WILLIAM R GREEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $230,667
- **Award type:** 5
- **Project period:** 1983-09-01 → 1994-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174451

## Citation

> US National Institutes of Health, RePORTER application 3174451, CELLULAR IMMUNITY TO ENDOGENOUS AKR LEUKEMIA VIRUSES (5R01CA036860-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174451. Licensed CC0.

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