Cutting edge: Introduction of an endopeptidase cleavage motif into a determinant flanking region of hen egg lysozyme results in enhanced T cell determinant display

The choice of which determinants of a whole Ag will be presented on tell su rface MHC class ii molecules after uptake and processing by APC is the resu lt of the interplay between structural characteristics of the Ag and the pr ocessing machinery of the APC. In this study, we demonstrate that introduct ion of a dibasic motif adjacent to a subdominant determinant enhances the p resentation of this determinant from the whole molecule. This is the first report showing that a single amino acid substitution in a whole Ag, designe d to introduce an endopeptidase recognition site, enhances display of class II-restricted determinants, most likely by creating a peptide chain cleava ge in the antigenic molecule. Our findings have important implications for the understanding of immunodominance and for vaccine design.