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UBC Theses and Dissertations
Molecular modulation of the lymphohaemopoietic system Jones, Amanda Tomlinson
Abstract
The immune system has evolved to enable recognition of a huge variety of antigens with high specificity via the production of large quantities of reactive antibody. The ability to direct both the specifities and the quantity of antibody production to derive antibodies with high affinities and pre-determined specificities has been an important advance in our exploration of the functions of the lymphohaemopoietic system. This thesis details two separate projects which have as their common theme the production of antibodies with defined specificities and their use as tools to further our understanding of the immune response. In the first part of the thesis, a monoclonal antibody against a cell surface glycoprotein is characterised and its target antigen identified as a unique isoform of CD43, likely the murine homologue of the T305 antigen. This isoform is developmentally regulated with differential patterns of expression on CD4 and CD8 lymphocytes and on activated cells. In addition the molecule is aberrantly expressed in a number of disease models including B-cell lymphoma, allograft rejection, graft-versus-host disease and the Ipr/fas mouse. The pattern of regulation of expression of the antigen is described in addition to studies detailing its biochemical structure, turnover, patterns of phosphorylation and intracellular associations. In addition some speculations as to the function of this specific isoform of CD43 are offered. In the second part of the thesis we describe the production and characterisation of polyclonal anti-peptide antibodies which react with the interleukin 3 (IL-3 molecule). These antibodies can be used as carrier molecules to prolong the in vivo half-life, alter the biodistribution and to enhance the bioactivity of IL 3 up to 7 fold. The characteristics of enhancing antibodies are defined, detailed pharmacokinetics are presented and some speculations as to the potential therapeutic uses and biological significance of such antibodies arising naturally in vivo are presented.
Item Metadata
| Title |
Molecular modulation of the lymphohaemopoietic system
|
| Creator | |
| Publisher |
University of British Columbia
|
| Date Issued |
1998
|
| Description |
The immune system has evolved to enable recognition of a huge variety of antigens with
high specificity via the production of large quantities of reactive antibody. The ability to direct both
the specifities and the quantity of antibody production to derive antibodies with high affinities and
pre-determined specificities has been an important advance in our exploration of the functions of
the lymphohaemopoietic system. This thesis details two separate projects which have as their
common theme the production of antibodies with defined specificities and their use as tools to
further our understanding of the immune response.
In the first part of the thesis, a monoclonal antibody against a cell surface glycoprotein is
characterised and its target antigen identified as a unique isoform of CD43, likely the murine
homologue of the T305 antigen. This isoform is developmentally regulated with differential
patterns of expression on CD4 and CD8 lymphocytes and on activated cells. In addition the
molecule is aberrantly expressed in a number of disease models including B-cell lymphoma,
allograft rejection, graft-versus-host disease and the Ipr/fas mouse. The pattern of regulation of
expression of the antigen is described in addition to studies detailing its biochemical structure,
turnover, patterns of phosphorylation and intracellular associations. In addition some speculations
as to the function of this specific isoform of CD43 are offered.
In the second part of the thesis we describe the production and characterisation of
polyclonal anti-peptide antibodies which react with the interleukin 3 (IL-3 molecule). These
antibodies can be used as carrier molecules to prolong the in vivo half-life, alter the biodistribution
and to enhance the bioactivity of IL 3 up to 7 fold. The characteristics of enhancing antibodies are
defined, detailed pharmacokinetics are presented and some speculations as to the potential
therapeutic uses and biological significance of such antibodies arising naturally in vivo are
presented.
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| Extent |
18477456 bytes
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| Genre | |
| Type | |
| File Format |
application/pdf
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| Language |
eng
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| Date Available |
2009-06-03
|
| Provider |
Vancouver : University of British Columbia Library
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| Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
|
| DOI |
10.14288/1.0088803
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| URI | |
| Degree | |
| Program | |
| Affiliation | |
| Degree Grantor |
University of British Columbia
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| Graduation Date |
1998-05
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| Campus | |
| Scholarly Level |
Graduate
|
| Aggregated Source Repository |
DSpace
|
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.