# HLA-D POLYMORPHISM AND DISEASE SUSCEPTIBILITY

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 1991 · $167,216

## Abstract

The long-range goal of this project is to understand how the
polymorphism of HLA class II D-region products influences
immune response and susceptibility to autoimmune disease such as
rheumatoid arthritis (RA) and insulin-dependent diabetes mellitus
(IDDM).  T cells recognize antigen in the context of HLA class II
molecules and allelic differences in class III molecules and
activate alloimmune T cells.  In this project, we will use cloned T
cells to define individual recognition sites on D-region products as
a means for identifying structural variants that might play a role
in immune response.  These recognition sites also might be
informative for the study of disease susceptibility.  There are
three components to our proposal.  First, we will generate T cell
clones that recognize the polymorphic sites on D-region molecules
associated with the DR3 and DR4 family of haplotypes.  These T
cell defined epitopes will be localized to specific HLA-D loci and
molecules, and eventually these recognition sites will be mapped
on individual HLA-D alpha and beta chains.  Second, we will
determine which of these T cell defined epitopes might be
associated with susceptibility to RA and IDDM.  Analysis with
pertinent T cell clones should yield definitive information about
the role of class II immune response genes as risk factors in these
diseases.  Third, T cells activated in vivo will be cloned from RA
patients to determine whether autoreactive T cells occur in blood
or synovial tissues, whether they recognize tissue-specific
antigens and whether they are specific for or restricted by any
particular HLA-D determinants.  These latter experiments may
lead to the development of a model for understanding the nature
of the immune response involved in the pathogenesis of RA.

## Key facts

- **NIH application ID:** 3159121
- **Project number:** 5R01AR039153-04
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **SAM.gov UEI:** HMSNCM57QNR5
- **Principal Investigator:** John Andrew Hansen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $167,216
- **Award type:** 5
- **Project period:** 1988-02-01 → 1993-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3159121

## Citation

> US National Institutes of Health, RePORTER application 3159121, HLA-D POLYMORPHISM AND DISEASE SUSCEPTIBILITY (5R01AR039153-04). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3159121. Licensed CC0.

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