# STRUCTURE OF IMMUNOLOGIC DETERMINANTS OF PROTEINS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1991 · $213,193

## Abstract

The major goal of this proposal is to contribute to a better
understanding of how antigens, class II MHC molecules and T cells
interact in the immune system.  The approach will be to delineate
the functional substructure of antigens and class II MHC
molecules.  For this purpose, the simple synthetic immunogen L-
tyrosine-p-azobenzenearsonate (ABA-tyr) will be used as a model,
against which we have now accumulated more than 50 murine T
cell cloned lines, including I-A/k-, I-E/k-, and I-A/b- restricted
lines from 3 inbred strains.

1.  The component of ABA-tyr tentatively identified as
comprising the structure that associates with Class II MHC
molecules (agretope) is the aromatic core (see Progress Report).
This inference will be tested by determining if phenylazotyrosine
does indeed function as a universal "carrier" for T cell epitopes.
2.  Amino acid residues critical for functional restriction
elements of class II molecules (histotopes) for ABA-tyr-specific T
cell clones will be identified using site-specific mutagenesis and
DNA transfection techniques.  These studies have been initiated
and look promising, although this approach clearly has
interpretational constraints which limit its utility.
3.  The capacity of ABA-tyr to interact in vitro with class II
molecules will be assessed using affinity-purified class II proteins.
It is hypothesized that ABA-tyr is immunogenic because it has a
relatively high affinity for a functional site on class II.  If a
specific site exists, it should be possible to affinity label it, and
an appropriately labelled ABA-tyr reagent will be used for this
purpose.  Identification of a binding site (candidate desetope) will
be extremely useful for functional studies by the site-specific
mutagenesis-DNA transfection approach.
4.  Individual T cell clones manifest complex functional activities,
including help, delayed hypersensitivity (DTH) and cytotoxicity,
all of which are Ia-restricted and antigen-dependent.  The
mechanism of killing these L3T4+ cell will be investigated and
their gene activation profiles with different types of antigen-
presenting cells (spleen cells, resting B cells, B cell tumors, and
transfected L cells) will be compared, using cDNA probes in RNA
dot blot experiments.  This should contribute to a better
understanding of the role of the APC in the regulation of
expression of manifold activities by individual T cells.

## Key facts

- **NIH application ID:** 3124252
- **Project number:** 5R01AI005664-28
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** JOEL W GOODMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $213,193
- **Award type:** 5
- **Project period:** 1977-01-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3124252

## Citation

> US National Institutes of Health, RePORTER application 3124252, STRUCTURE OF IMMUNOLOGIC DETERMINANTS OF PROTEINS (5R01AI005664-28). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3124252. Licensed CC0.

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