# COMPARATIVE MOLECULAR STUDIES ON HLA ANTIGENS

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1987 · $156,957

## Abstract

The HLA class II or Ia molecules are mediators of the immune response, and
have been associated with predisposition to certain diseases.  Structural
characterization indicates that human Ia molecules consist of a 34,000d
Alpha chain glycoprotein associated non-covalently with a 29,000d Beta
chain glycoprotein, both of which are encoded by the HLA complex.  This
Alpha, Beta heterodimer is associated with several "invariant" chain
glycoproteins creating an Ia "oligomeric complex.  We recently discovered
that the Ia oligomeric" complex contains a previously undescribed 40-7-Kd
chondroitin-sulfate proteoglycan component, and that the Ia Alpha and Beta
chains can be sulfated.  The broad objectives of this proposal are to
structurally and biologically characterize the Ia associated proteoglycan
component, and to elucidate the physiology of Alpha and Beta chain
sulfation.  We will radiolabel normal human lymphoid cells and
lymphoblastoid cell lines with 35SO4 and 3H-amino acid precursors.  The
labeled molecules will be solubilized in non-ionic detergent, purified by
anion-exchange chromatography, immunoprecipitated with anti-human Ia
antibodies and analyzed by 1- and 2-D PAGE and sizing chromatography.  The
core-protein of the proteoglycan will be analyzed by tryptic peptic peptide
mapping and partial amino acid sequencing.  Using these techniques, we will
determine the cellular distribution of the 40-70Kd proteoglycan in both Ia+
and Ia- cells of lymphoid and non-lymphoid tissues.  We will determine the
structural features of the proteoglycan component including the size of the
core protein, the similarity, if any, of the core protein to known Ia
glycoproteins, and the size and number of the glycosaminoglycan
components.  We will ascertain the fraction of Ia molecules associated with
the proteoglycan, when and where the association takes place, the transit
time of the proteoglycan to the cell surface, and the effect of
proteoglycan synthesis inhibitors on the synthesis and plasma membrane
expression of Ia.  We will determine if removal or blockade of cell surface
chondroitin sulfate interferes with binding during cellular interactions.
The sulfate-bearing moiety on 35SO4-labeled Ia Alpha and Beta chains will
be identified by pronase digestion, followed by HPLC and electrophoretic
analyses.  Because sulfation of Ia may play a role in cellular regulatory
events, we will determine if reaction of Ia bearing cells with anti-Ia
antibodies and mitogens alters sulfation of the Ia Alpha and Beta chains.

## Key facts

- **NIH application ID:** 3128311
- **Project number:** 5R01AI018925-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** BENJAMIN D SCHWARTZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $156,957
- **Award type:** 5
- **Project period:** 1982-07-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128311

## Citation

> US National Institutes of Health, RePORTER application 3128311, COMPARATIVE MOLECULAR STUDIES ON HLA ANTIGENS (5R01AI018925-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128311. Licensed CC0.

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