title: Going Pro to enhance T-cell immunogenicity: easy as π?
abstract: 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.
authors.affiliation: Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Hickman
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
mesh_terms: D000818:Animals; D064532:Histocompatibility Antigen H-2D / Q000276:immunology*; D011392:Proline / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D058951:gp100 Melanoma Antigen / Q000276:immunology*
chemical_list: D064532:Histocompatibility Antigen H-2D; D011948:Receptors, Antigen, T-Cell; D058951:gp100 Melanoma Antigen; D011392:Proline
keywords: Altered peptide ligand; MHC class I; Peptide; Tumor-associated Ag