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. >2 h 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.

► Low tapasin facilitation and high stability defines immunogenic peptides.
► The thresholds defining tapasin facilitation and stability varies in a HLA-I allomorph specific manner.
► The dissociation of a set of SYFPEITHI peptide–HLA–A∗02:01 and SYFPEITHI peptide–HLA–B∗08:01 complexes is biphasic at 37 °C.