Stability of peptide-HLA-I complexes and tapasin folding facilitation--tools to define immunogenic peptides

Only a small fraction of the peptides generated inside the cell end up being presented by HLA-I on the cell surface. High stability of peptide-HLA-I complexes and a low HLA-I tapasin-facilitation have been proposed to predict immunogenicity. We here set out to investigate if these parameters correlated and defined immunogenic peptides. Both peptide-HLA-B(?)08:01 and peptide-HLA-A(?)02:01 complexes showed small differences in tapasin-facilitation and larger differences in stability. This suggests that the stability of immunogenic peptide-HLA-I complexes vary above an HLA-I allomorph dependent lower limit (e.g. >2h for HLA-A(?)02:01), immunogenicity predicted by tapasin-facilitation may be defined by an equally allomorph unique upper value (e.g. tapasin-facilitation <1.5 for HLA-A(?)02:01), and variation above the stability-threshold does not directly reflect a variation in tapasin-facilitation.