See accompanying article by Uchtenhagen et al.
Going Pro to enhance T-cell immunogenicity: Easy as π?
Version of Record online: 24 OCT 2013
© 2013 This article is a U.S. Government work and is in the public domain in the USA.
European Journal of Immunology
Volume 43, Issue 11, pages 2814–2817, November 2013
How to Cite
Hickman, H. D. and Yewdell, J. W. (2013), Going Pro to enhance T-cell immunogenicity: Easy as π?. Eur. J. Immunol., 43: 2814–2817. doi: 10.1002/eji.201344095
- Issue online: 20 NOV 2013
- Version of Record online: 24 OCT 2013
- Manuscript Accepted: 4 OCT 2013
- Manuscript Received: 18 SEP 2013
- Manuscript Revised: 18 SEP 2013
- National Institutes of Allergy and Infectious Diseases
- Altered peptide ligand;
- MHC class I;
- Tumor-associated Ag
MHC class I molecules bind intracellular oligopeptides and present them on the cell surface for CD8+ T-cell activation and recognition. Strong peptide/MHC class I (pMHC) interactions typically induce the best CD8+ T-cell responses; however, many immunotherapeutic tumor-specific peptides bind MHC with low affinity. To overcome this, immunologists can carefully alter peptides for enhanced MHC affinity but often at the cost of decreased T-cell recognition. A new report published in this issue of the European Journal of Immunology [Eur. J. Immunol. 2013. 43:3051–3060] shows that the substitution of proline at the third residue (p3P) of a common tumor peptide increases pMHC affinity and complex stability while enhancing T-cell receptor recognition. X-ray crystallography indicates that stability is generated through newly introduced CH-π bonding between p3P and a conserved residue (Y159) in the MHC heavy chain. This finding highlights a previously unappreciated role for CH-π bonding in MHC peptide binding, and importantly, arms immunologists with a novel and possibly general approach for increasing pMHC stability without compromising T-cell recognition.