# ANALYSIS OF H-2 MUTANT STRAINS

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1987 · $207,908

## Abstract

This proposal continues our studies on class I molecules and how mutation
of the genes that encode these molecules affects T cell recognition.  One
mechanism to explain the multiple base changes seen in H-2Kbm mutant genes
is gene conversion.  The Q10 gene has the bases found in the mutant H-2Kbm1
gene and has been proposed to be the donor gene for this mutation.  We will
generate CTL against Qa antigens, including those not normally expressed
(such as Q10), and determine the relationship between these antigens and
H-2Kbm molecules (and other class I molecules).  Interferon has been shown
to up-regulate the expression of class I antigens.  We will demonstrate
that interferon does not up-regulate some Qa antigens.  Using domain
shuffled Qa/class I antigens, we will determine the region of class I genes
that allows for interferon inducibility and determine the role of
interferon in augmenting CTL activity.  The structure of Qa and TL antigens
is very similar to that of the class I molecules, H-2K, D, and L.
Nevertheless, the former molecules do not serve as restricting elements for
antigen specific CTL.  Since domain shuffled Qa and TL antigens are
expressed on transfected L cells at relatively high density, we will test
the ability of these molecules to function as target molecules for
antigen-specific H-2 restricted CTL.  In collaborative studies, these Qa
and Tla exon shuffled genes will be introduced into mouse ova and the
transgenic mice will be tested for their ability to use these molecules as
restricting elements for antigen-specific CTL.  Site specific mutagenesis
of MHC genes allows for a determination of what structures affect CTL
recognition.  We will determine the fine specificity of anti-H-2Ld CTL
clones by testing their activity against several H-2Ld mutants.  In
collaborative studies, the structure of the T-cell receptor genes will be
determined.  The role of carbohydrate on MHC molecules in affecting CTL
recognition will be determined, as will the affect of removing the entire
cytoplasmic portion of the molecule.  Finally, the structural components of
VSV will be analyzed to determine 1) which molecules encoded by the virus
are recognized by CTL and 2) whether mice with differing H-2 alleles
respond to different viral components.

## Key facts

- **NIH application ID:** 3125371
- **Project number:** 5R01AI013111-12
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** JAMES M FORMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $207,908
- **Award type:** 5
- **Project period:** 1976-08-01 → 1991-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125371

## Citation

> US National Institutes of Health, RePORTER application 3125371, ANALYSIS OF H-2 MUTANT STRAINS (5R01AI013111-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125371. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*