作者
Ji-Li Chen, Guillaume Stewart-Jones, Giovanna Bossi, Nikolai M Lissin, Linda Wooldridge, Ed Man Lik Choi, Gerhard Held, P Rod Dunbar, Robert M Esnouf, Malkit Sami, Jonathan M Boulter, Pierre Rizkallah, Christoph Renner, Andrew Sewell, P Anton van der Merwe, Bent K Jakobsen, Gillian Griffiths, E Yvonne Jones, Vincenzo Cerundolo
发表日期
2005/4/4
期刊
The Journal of experimental medicine
卷号
201
期号
8
页码范围
1243
出版商
The Rockefeller University Press
简介
Analogue peptides with enhanced binding affinity to major histocompatibility class (MHC) I molecules are currently being used in cancer patients to elicit stronger T cell responses. However, it remains unclear as to how alterations of anchor residues may affect T cell receptor (TCR) recognition. We correlate functional, thermodynamic, and structural parameters of TCR–peptide–MHC binding and demonstrate the effect of anchor residue modifications of the human histocompatibility leukocyte antigens (HLA)–A2 tumor epitope NY–ESO-1 157–165–SLLMWITQC on TCR recognition. The crystal structure of the wild-type peptide complexed with a specific TCR shows that TCR binding centers on two prominent, sequential, peptide sidechains, methionine–tryptophan. Cysteine-to-valine substitution at peptide position 9, while optimizing peptide binding to the MHC, repositions the peptide main chain and generates subtly …
引用总数
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JL Chen, G Stewart-Jones, G Bossi, NM Lissin… - The Journal of experimental medicine, 2005