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

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Stability of peptide-HLA-I complexes and tapasin folding facilitation - tools to define immunogenic peptides. / Geironson Ulfsson, Linda; Roder, Gustav; Paulsson, Kajsa M.

In: FEBS Letters, Vol. 586, No. 9, 2012, p. 1336-1343.

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T1 - Stability of peptide-HLA-I complexes and tapasin folding facilitation - tools to define immunogenic peptides

AU - Geironson Ulfsson, Linda

AU - Roder, Gustav

AU - Paulsson, Kajsa M

PY - 2012

Y1 - 2012

N2 - 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. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

AB - 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. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

KW - Tapasin

KW - MHC-I

KW - Peptide

KW - Stability

KW - Vaccine

U2 - 10.1016/j.febslet.2012.03.045

DO - 10.1016/j.febslet.2012.03.045

M3 - Article

VL - 586

SP - 1336

EP - 1343

JO - FEBS Letters

T2 - FEBS Letters

JF - FEBS Letters

SN - 1873-3468

IS - 9

ER -