# GENETIC REGULATION OF LYMPHOID DIFFERENTIATION ANTIGENS

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 1989 · $214,265

## Abstract

HLA Class II cell surface molecules have important roles in cell
interactions involved in immune responses, and specific alleles of Class II
antigens appear to confer susceptibility to certain diseases, probably by
virtue of their immune functions.  HLA Class II genes are regulated in a
complex manner, being constitutively expressed, inducibly expressed, or not
expressed, depending on the cell type examined and its stage of
differentiation.  This application proposes various molecular and genetic
approaches to study Class II gene regulation.  Somatic cell hybrids of HLA
Class II expressing and non-expressing and inducible cell types and mutants
will be made in various combinations to define by complementation analysis
the number of factors, pathways or subunits by which Class II expression is
regulation.  Preliminary evidence from this laboratory suggests that their
is a transactive positive regulator of Class II genes which acts
transcriptionally. A major aim of this proposal is to characterize the
putative regulator of Class II expression, and its site and mode of
action.  Assays for the proposed transactive regulator will be developed so
that the regulator can be characterized.  Isolated mutants with low levels
of a single Class II gene mRNA will be studied to determine whether the
lesions are transcriptional.  Transcription defective Class II genes and
the normal genes from which they derived will be cloned.  The ability of
the regulatory molecule to bind to the normal and transcription-defective
mutant genes and to induce DNase I hypersensitivity will be determined.
Genomic clones of mutant genes with transcriptional lesions will be
partially sequenced to map the affected nucleotide positions.  The other
major goal of this application is to clone the gene coding for the Class II
transactive regulator, to determine how its gene product operates, and to
map the sequences it binds in to or around HLA Class II genes.

## Key facts

- **NIH application ID:** 3126771
- **Project number:** 5R01AI016689-10
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **SAM.gov UEI:** HD1WMN6945W6
- **Principal Investigator:** DONALD A PIOUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $214,265
- **Award type:** 5
- **Project period:** 1980-06-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126771

## Citation

> US National Institutes of Health, RePORTER application 3126771, GENETIC REGULATION OF LYMPHOID DIFFERENTIATION ANTIGENS (5R01AI016689-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126771. Licensed CC0.

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