Slight alterations in peptide sequence alter the peptide–HLA–TCR interaction and affect T cell priming.

A single amino acid change in a tumor-derived peptide results in the priming of a bigger and better T cell response upon vaccination, according to a study by Chen et al. on page 1243. Thus, results obtained with the original peptide, which is in phase I clinical trials as an anticancer vaccine, may be further enhanced by using the modified peptide.

Single amino acid changes in peptides can either enhance or inhibit activation of the T cells whose T cell receptors (TCRs) bind the peptide–HLA complex. Structural alterations in the HLA–peptide–TCR complex are thought to cause these functional changes, although how structural changes modify the signaling events inside the T cell is not completely understood.

To address this question, Chen et al. crystallized peptide–HLA–TCR complexes using either a wild-type tumor...

The Rockefeller University Press
2005
The Rockefeller University Press
2005
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