# STRUCTURE AND GENETICS OF ANTIBODY VARIABLE REGIONS

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 1987 · $122,484

## Abstract

The long-term goal of studies described in this application is to
understand the diversification mechanisms which enable vertebrate organisms
to synthesize antibodies specific for a seemingly unlimited variety of
pathogens and other foreign substances.  As a model system, the antibody
response of inbred strain A mice to the cell wall carbohydrate (A CHO) of
group A streptococci, the causative agent of strep throat, is being
analyzed.  The proposed research focuses on determining:  (1) the number of
distinct germ-line genes that encode anti-A CHO antibodies; (2) the
contribution of combinatorial joining of genes to the diversity among
anti-A CHO antibodies; (3) the extent to which somatic mutation contributes
to diversity; (4) the influence of ontogeny, antigenic stimulation and
isotype switching on diversification processes; and (5) structural
correlates of antibody specificity and idiotypy.

An estimate of the number of antibody variable region genes that encode
anti-A CHO antibodies is obtained by comparative restriction mapping of DNA
from anti-A CHO hybridomas utilizing Southern blot hybridizations with J
gene probes to visualize rearranged, expressed genes.  The initial data
obtained with J probes will be verified with single-copy probes specific
for the V gene of interest.  The hybridomas are representative of primary
and secondary antibody responses (antigenic stimulation), IgM and IgG3
producers (isotype switching), and antibody responses of young and adult
mice (ontogeny).  Using conventional molecular biological procedures, the
variable region genes expressed by the hybridomas will be isolated and
their nucleotide sequences determined.  The corresponding germ-line genes
will be isolated from embryonic DNA and sequenced.  Analysis of these
nucleotide sequences will allow a definitive assessment of mechanisms
utilized in the diversification of anti-A CHO antibodies.  Our approach to
establishing structure-function correlates is to obtain hybridomas which
express appropriate VH and VL genes, but fail to express functions
associated with these genes, A CHO-binding and idiotypy.  The nucleotide
sequences of these "variant" V regions will be determined to identify
"lesions" responsible for loss of function.

## Key facts

- **NIH application ID:** 3170394
- **Project number:** 5R01CA032497-06
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **SAM.gov UEI:** MQE2JHHJW9Q8
- **Principal Investigator:** Janet M. Stavnezer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $122,484
- **Award type:** 5
- **Project period:** 1981-09-30 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170394

## Citation

> US National Institutes of Health, RePORTER application 3170394, STRUCTURE AND GENETICS OF ANTIBODY VARIABLE REGIONS (5R01CA032497-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170394. Licensed CC0.

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