# CELLULAR IMMUNITY TO ENDOGENOUS AKR LEUKEMIA VIRUSES

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1990 · $165,024

## Abstract

The long range goals of the laboratory are to define in detail the
antigenic requirements for induction, the specificity for H-2 and
virus-associated determinants, and the genetic control of both the
induction and the specificity of cytotoxic T lymphocyte (CTL) responses to
weakly immunogenic antigens on syngeneic tumors induced by AKR/Gross MuLV.
In addition we will investigate one possible mechanism of tumor escape from
immune surveilance.  Namely, some MuLV-induced tumors may be resistant to
the ability of gamma interferon to augment cell surface H-2 expression.
Although study of the high-leukemic AKR strain is the ultimate goal, this
strain represents a very complex situation.  Therefore, initial studies
have dealt with the low-leukemic C57BL/6 (B6) strain which is genetically
resistant to Gross virus-induced leukemia, but for which teh syngeneic
tumor cell prototype for the definition of the Gross cell surface antigen
(GCSA) exists.  These studies resulted in the description of a scheme for
raising H-2Kb restricted cytotoxic T cells specific for that subclass of
endogenous AKR/Gross virus-induced leukemias which display GCSA.  The
present proposal would first further define this system so that a firm
experimental basis would be obtained for the investigation of other strains
of mice.  Then, various F1, congenic, H-2 recombinant inbred and H-2Kb
mutant mice, some of whose genotypes reflect differing contributions by
donor strains of mice of high-leukemic phenotype, will be employed.  Such
an approach will extend our previous experiments which have shown the
influence of both H-2 encoded genes and genes controlling viral antigen
expression on antiviral CRL responsiveness.  These studies thus ultimately
serve as an approach towards the in-depth study of CTl responses in
high-leukemic mice.  Thus, a complicated, perhaps specifically
immunodepressed system such as the AKR mouse can be systematically
dissected by gradually building from a known positive system.  With
knowledge of the effects of individual genetic loci and viral influences,
the AKR mouse can better be approached to determine if it is indeed
nonresponsive to its spontaneously arising leukemias, and if so, how the
system can be manipulated to promote an effective immune response.
Definition of strageties to augment cell mediated responses to these weakly
immunogenic antigens may have broad applicability to immune intervention to
tumors in higher species.

## Key facts

- **NIH application ID:** 3174450
- **Project number:** 5R01CA036860-08
- **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:** 1990
- **Award amount:** $165,024
- **Award type:** 5
- **Project period:** 1983-09-01 → 1991-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174450

## Citation

> US National Institutes of Health, RePORTER application 3174450, CELLULAR IMMUNITY TO ENDOGENOUS AKR LEUKEMIA VIRUSES (5R01CA036860-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174450. Licensed CC0.

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