# ANALYSIS OF H-2 MUTANT STRAINS

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1992 · $145,397

## Abstract

This proposal represents a continuation of our studies examining the
structure-function of class I molecules of the MHC.  Three issues will be
addressed.

The first will determine the role of the alpha3 domain of class I in the
positive and negative selection of the T cell receptor (TcR) repertoire.
We will utilize a laboratory engineered class I molecule, LQ3, which is the
Ld in the alpha1, alpha2, TM, and cytoplasmic domains but derives its
alpha3 domain from Q7b.  Our published and preliminary data demonstrates
that LQ3 binds Ld restricted peptides and is recognized by CD8 independent
but not CD8 dependent cytotoxic T lymphocytes (CTL).  The expression of LQ3
in C3H transgenic (TG) animals does not allow for the generation of
cytomegalovirus (MCMV) specific Ld-restricted CTL, nor does it permit
complete negative selection of anti-Ld alloreactive CTL.  We will generate
TG mice that express a TcR for Ld-MCMV and mate these animals to existing
C3H.Ld and C3H.LQ3 TG mice to follow the fate of such cells.  The failure
of CTL to recognize LQ3 is presumably due to the inability of CD8 to
interact with its ligand in the Q7 alpha3 domain.  We will use a variety of
CD8 <-> class I binding assays to characterize this defect.

The second issue will address the relationship between low affinity (1o)
and high affinity (2o) receptor alloreactive CTL.  We will utilize the TcRs
from a representative clone of each of these CTL to generate TcR TG mice.
This will allow us to characterize the precursor-product relationship
between such clones with regard to receptor avidity, CD8 expression,
lymphokine secretion, and dependence of CD4 T helper activity.

The third issue will focus on Qa-2 as an antigen presenting molecule.  We
will determine the TcR V gene usage of CTL specific for Q6 and Q7, the 2
major Qa-2 encoded antigens.  We will determine the sequence of the Q6
gene, which is the major target molecule for Qa-2 specific CTL and
establish whether these Qa molecules present a limited array of peptides.

## Key facts

- **NIH application ID:** 3125369
- **Project number:** 2R01AI013111-16A1
- **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:** 1992
- **Award amount:** $145,397
- **Award type:** 2
- **Project period:** 1976-08-01 → 1997-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125369

## Citation

> US National Institutes of Health, RePORTER application 3125369, ANALYSIS OF H-2 MUTANT STRAINS (2R01AI013111-16A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125369. Licensed CC0.

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