# ACTIVATION OF THE COMPLEMENT SYSTEM

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1988 · $180,453

## Abstract

Activation of the complement system results in a selective and control
fragmentation of the C4 and C3 molecules via the classical, or the
classical and alternative pathways respectively.  Interaction of fragments
of these two molecules with antigen-antibody complexes and with surface
receptors on different cell types serve to modulate complement-dependent
functions.  Although a great deal of knowledge has been accumulated on the
alternative pathway, the same information relating to the classical pathway
is less complete.  This application proposes studies aimed primarily at
delineating some structural and functional aspects of the proteins involved
in the formation and some structural and functional aspects of the proteins
involved in the formation and function of the classical pathway C3
convertase.  Specifically, we plan to 1) Further characterize the major
cleavage fragments of C4 produced during activation and inactivation of the
molecule.  The fragments will be isolated to homogeneity and subjected to
chemical analysis.  2) Analysis of the conformational changes accompanying
the enzymatic conversion and degradative inactivation of C4 by various
methods.  These studies will use differential surface labeling which will
allow the identification of distinct regions of the molecule involved in
these functional changes.  3) Investigation of the structural requirements
for the interaction of the control proteins, C4-bp and I, with fluid phase
and surface bound C4b.  4) The observation of an abnormal protein seen in
humans serum under pathological conditions, C4 nephritic factor, has
prompted studies to identify a protein in normal serum capable of
stabilizing the C4b2a enzyme.  The identification of this protein would
complete the analogies to the formation, function and regulation of the
classical and alternative C3 convertases.  A second part of the application
to which the above studies are of interest involves the activation of the
complement system by IgA and IgM containing immune complexes.  In addition,
the mechanisms of complement activation by a non-immunologic mechanism
using phototoxic chemicals will be investigated.

## Key facts

- **NIH application ID:** 3129583
- **Project number:** 5R01AI020067-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** IRMA GIGLI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $180,453
- **Award type:** 5
- **Project period:** 1982-09-15 → 1989-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129583

## Citation

> US National Institutes of Health, RePORTER application 3129583, ACTIVATION OF THE COMPLEMENT SYSTEM (5R01AI020067-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129583. Licensed CC0.

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