# STRUCTURAL-FUNCTIONAL ANALYSIS OF MHC CLASS II MOLECULES

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 1992 · $198,521

## Abstract

The mandatory formation of a trimolecular complex consisting of
processed antigen, MHC class II molecule and T-cell receptor for
activation of helper T cells has become one of the paradigms of
modern immunology.  This application proposes to examine the
role of one of the components of this complex, the MHC class II
molecule (Ia antigen), in this process.  These studies will exploit
structure-function analysis of the Ia antigens as well as make
extensive use of anti-class II monoclonal antibodies and chemical
crosslinkers.  The overall goal of defining the functional sites of
the I-Ak molecule that are involved in the interaction of the class
II molecule with peptides (representing processed antigen) and
with the T-cell receptor will be accomplished through the
completion of four specific aims.  First, the epitopes detected by
the monoclonal antibodies will be mapped using chemical
crosslinking and protein microsequence analysis to identify those
portions of the I-Ak molecule in contact with the monoclonal
antibodies or in close proximity to its binding site.  Second, anti-I-
Ak monoclonal antibodies and mutant I-Ak molecules will be
employed to locate and to define the biochemical properties of
the peptide-binding and T-cell receptor-contacting sites of the I-
Ak molecule.  Third, synthetic peptides corresponding to the
hypervariable region sequences of the A alpha and A beta chains
will be used to probe the antigen/I-A/T cell receptor interactions.
Studies under this specific aim will determine the effect these
peptides have no antigen binding and on antigen presentation by I-
A molecules and will attempt to establish the mechanism(s) by
which the hypervariable region peptides act.  Fourth, chemical
crosslinkers and protein microsequencing will be employed to
locate the portions of the I-A molecule that make contact with
the bound peptide antigen.  The proposed studies derive medical
significance from the fact that the human class II molecules,
HLA-DR, -DP and -DQ show clear associations with certain
disease states in man.  Recent studies have suggested that allelic
variation in hypervariable regions homologous to those studied in
the present application may explain these associations.  Clearly,
the understanding of the structure-function relationships of the
class II molecules should facilitate the design of rational
treatments and/or preventatives for these HLA-associated
diseases.

## Key facts

- **NIH application ID:** 3174278
- **Project number:** 5R01CA036700-10
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **SAM.gov UEI:** VLQKFEEJ3NE9
- **Principal Investigator:** JOHN H FREED
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $198,521
- **Award type:** 5
- **Project period:** 1983-07-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174278

## Citation

> US National Institutes of Health, RePORTER application 3174278, STRUCTURAL-FUNCTIONAL ANALYSIS OF MHC CLASS II MOLECULES (5R01CA036700-10). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3174278. Licensed CC0.

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