Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein

Processing of endogenously synthesized proteins generates short
peptides that are presented by MHC class I molecules to CD8 T
lymphocytes. Here it is documented that not only the sequence of
the presented peptide but also the residues by which it is flanked
in the protein determine the efficiency of processing and
presentation. This became evident when a viral sequence of proven
antigenicity was inserted at different positions into an unrelated
carrier protein. Not different peptides, but different amounts of
the antigenic insert itself were retrieved by isolation of
naturally processed peptides from cells expressing the different
chimeric proteins. Low yield of antigenic peptide from an
unfavorable integration site could be overcome by flanking the
insert with oligo-alanine to space it from disruptive neighboring
sequences. Notably, the degree of protection against lethal virus
disease related directly to the amount of naturally processed
antigenic peptide.