Projects per year
Abstract
Protein phosphorylation generates a source of phosphopeptides that are presented by major histocompatibility complex class I molecules and recognized by T cells. As deregulated phosphorylation is a hallmark of malignant transformation, the differential display of phosphopeptides on cancer cells provides an immunological signature of 'transformed self'. Here we demonstrate that phosphorylation can considerably increase peptide binding affinity for HLA-A2. To understand this, we solved crystal structures of four phosphopeptide-HLA-A2 complexes. These identified a novel peptide-binding motif centered on a solvent-exposed phosphate anchor. Our findings indicate that deregulated phosphorylation can create neoantigens by promoting binding to major histocompatibility complex molecules or by affecting the antigenic identity of presented epitopes. These results highlight the potential of phosphopeptides as novel targets for cancer immunotherapy.
Original language | English |
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Pages (from-to) | 1236-43 |
Number of pages | 8 |
Journal | Nature Immunology |
Volume | 9 |
Issue number | 11 |
Early online date | 5 Oct 2008 |
DOIs | |
Publication status | Published - 1 Nov 2008 |
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Dive into the research topics of 'Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self.'. Together they form a unique fingerprint.Projects
- 3 Finished
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Probing Novel Modes of Molecular Recognition by the Leukocyte Immunoglobulin-Like Receptor Family
Willcox, B., Martin, A. & Moss, P.
Biotechnology & Biological Sciences Research Council
5/07/07 → 4/01/11
Project: Research Councils
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The Development of Cellular Therapy for the Correction of CMV-Specific Immunodeficiency After Stem Cell Transplantation
Cobbold, M.
1/07/03 → 31/07/09
Project: Research Councils
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A Biophysical Approach Towards Exploiting the Clinical Potential of Alloreactive T-Cell Recognition
Young, L.
3/03/03 → 28/02/07
Project: Research Councils