http://www.eurekalert.org/pub_releases/2001-08/joci-hta071101.php
Public release date: 1-Aug-2001
Molecular mimicry, structural similarity
between viral proteins and host molecules, is thought to explain the genesis
of self-specific antibodies in autoimmune disease.
Here, Chackerian and coworkers propose
a means to turn this pathological response to clinical advantage. The same
group previously showed that one of the major capsid proteins of bovine
papillomavirus can assemble spontaneously, even without other viral components,
to form a population of viruslike particles (VLPs).
They have now developed a versatile
technique by which peptides can be conjugated to VLPs, a form in which
even normally nonimmunogenic self epitopes can elicit high titers of specific
antibodies.
Vaccination of mice with VLP-conjugated
TNF-a peptides yields IgGs that inhibit this cytokine and can block or
delay the onset of experimentally induced arthritis — a disease process
that is driven by high levels of TNF-a. This robust immune response, as
compared with that seen in control vaccinations with unconjugated TNF-a
peptides, seems to reflect relatively late events in the activation of
self-specific B cells.
IgM titers are not dramatically different
when animals are exposed to the epitope in either conjugated or unconjugated
form, but at some point during or after their commitment to IgG production,
mature B cells become strongly influenced by the structural context of
the epitope.
Presumably, VLP conjugation could
be used to generate neutralizing antibodies to, and provide long-term suppression
of, a variety of self or foreign molecules.
Contact: Mark Livingston
Journal of Clinical Investigation
mark@the-jci.org
734-222-6050