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Study reveals current multi-component vaccines may need reworking
Date:5/7/2009

se in the presence of other immunodominant peptides. Sant's team increased the ability of a cryptic peptide to hold onto MHC class II proteins by making changes to one or more of their four "anchor residues" responsible for binding into the pocket on the MHC Class II proteins, changes that sustained T cell responses.

In addition, peptide vaccines traditionally address just one half of the adaptive immunity system, the cell mediated/T cell system concerned with attacking pathogens once they have already infected their target cells. One of the principle roles of helper CD4+ T cells is to turn on CD8 "killer" T cells that sense infected cells and destroy them before a virus can use the cell as a virus factory. Peptide vaccines work by targeting only T cells, which explains why they have not been widely used against pathogens like the flu viruses, which spend part of their lifecycle in the space between cells. Those invaders must be addressed by antibodies, which directly glom onto invaders, and tag them for further immune attack.

Sant argues that understanding immunodominance has become even more important in light of recent publications that show strong T cell responses to a peptide have a role in the reactions that causes B cells to start mass producing antibodies as well. Activated T cells move into "the B cell area" of the lymph node and encourage B cells to start making antibodies. Recent studies have also shown that this process may be most efficient for stable peptide:MHC class II complexes. Kinetic stability may influence both the B and T cell aspects of the adaptive immune system.

The studies were performed within the Department of Microbiology and Immunology and the David H. Smith Center for Vaccine Biology and Immunology at the University of Rochester Medical Center, and funded by the National Institutes of Health.

"Evolution may have chosen kinetic stability as the way in which it decides which pieces of disease-cau
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-273-1757
University of Rochester Medical Center
Source:Eurekalert

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