Proline substitution independently enhances H-2D(b) complex stabilization and TCR recognition of melanoma-associated peptides.

Hannes Uchtenhagen, Esam T Abualrous, Evi Stahl, Eva B Allerbring, Marjolein Sluijter, Martin Zacharias, Tatyana Sandalova, Thorbald van Hall, Sebastian Springer, Per-Åke Nygren, Adnane Achour

European journal of immunology 2013 Nov

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The immunogenicity of H-2D(b) (D(b)) restricted epitopes can be significantly increased by substituting peptide position 3 to a proline (p3P). The p3P modification enhances MHC stability without altering the conformation of the modified epitope allowing for T-cell cross-reactivity with the native peptide. The present study reveals how specific interactions between p3P and the highly conserved MHC heavy chain residue Y159 increase the stability of D(b) in complex with an optimized version of the melanoma-associated epitope gp10025-33 . Furthermore, the p3P modification directly increased the affinity of the D(b)/gp10025-33 -specific T-cell receptor (TCR) pMel. Surprisingly, the enhanced TCR binding was independent from the observed increased stability of the optimized D(b)/gp10025-33 complex and from the interactions formed between p3P and Y159, indicating a direct effect of the p3P modification on TCR recognition. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Citation

Hannes Uchtenhagen, Esam T Abualrous, Evi Stahl, Eva B Allerbring, Marjolein Sluijter, Martin Zacharias, Tatyana Sandalova, Thorbald van Hall, Sebastian Springer, Per-Åke Nygren, Adnane Achour. Proline substitution independently enhances H-2D(b) complex stabilization and TCR recognition of melanoma-associated peptides. European journal of immunology. 2013 Nov;43(11):3051-60