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

s cause a T cell expansion after the complexes have arrived at the cell surface, as well as through DM editing inside the cell. A peptide's persistence at the cell surface also controls the ability of CD4 T cells to continue to expand. Importantly, this additional level of control over immunodominance by stability was only detected when many peptides were present, and were "competing" to see which would trigger a T cell response.

The team also found that low-stability peptide:class II complexes support the initial priming and expansion of CD4 T cells, but the expansion is "strikingly aborted" in the presence of competitive T cell responses to immunodominant peptides. Peptides that fall off of MHC class II molecules too quickly fail to sustain the expansion.

"What we saw is that if a dendritic cell offers weak or unstable peptides alone, T cell responses move forward," said Sant, the study's lead author. "But if we offered weak peptides in the presence of immunodominant ones, the weak peptides trigger an expansion at first, but then the response stalls. This competitive aspect is a new and has profound implications for vaccine design."

While still a theory, Sant speculates that losses in some T cell responses can be explained in part by trogocytosis, a process where T cells "steal" key pieces of the dendritic cell each time they dock onto it as a step in their decision to start expanding. Stolen pieces may include the peptide at hand, the MHC class II protein and so called co-stimulatory molecules. If there are many more of immunodominant peptide-MHC class II complexes initially displayed by the dendritic cell due to DM editing, and if cryptic peptides are falling off the MHC class II complex at a faster rate, and if T cells poach from the peptide-bearing dendritic cell with each pass, dominant peptides would continue activating T cells long after responses to cryptic peptides had petered out.

Without causing an actual infection
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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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