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

ptides on the cell's surface for consideration by T cells gathered there. Activated T cells begin dividing, which greatly increase their number, until they become capable of the destroying the pathogen in question when exposed to high enough levels of the peptide representing it.

Andrea Sant, Ph.D., professor within the David H. Smith Center for Vaccine Biology and Immunology at the University of Rochester Medical Center, published a July 2005 article in the journal Immunity which revealed the quality that confers immunodominance on a peptide to be the strength and lifespan (kinetic stability) of its bond to the MHC class II protein. Kinetic stability determines whether, in the face of competing reactions, a peptide:MHC class II complex can accumulate at the surface of the dendritic cell, and then remain intact long enough to sustain T cell expansion. Dr. Sant's team found that immunodominant peptides held onto to MHC molecules ten to one hundred times longer than nondominant, or "cryptic," peptides because they fit together better. In the years since, Sant and colleagues have determined how the kinetic stability of the MHC:peptide bond has its effect.

In 2006, she published a study in the Journal of Experimental Medicine that found an enzyme called human leukocyte antigen-DM opens pockets on the MHC class II molecule for a given peptide to fit into it before the complex heads to the cell's surface to recruit T cells. Within dendritic cells (and related cell types that present peptides to immune cells), DM was found to favor peptides with highly stable MHC interactions, a process dubbed "DM editing." Sant's team found kinetically stable peptide-MHC complexes arrived at the cell surface as much as 100 times more often than cryptic peptides, and thought DM editing was solely responsible for determining immunodominance.

The current paper found, however, that the persistence of peptide-MHC Class II bonds also determines which peptide
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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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