期刊
NATURE IMMUNOLOGY
卷 9, 期 11, 页码 1236-1243出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1660
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资金
- US Public Health Service [AI20963, AI33993]
- Medical Research Council
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council
- Sidney Kimmel Foundation
- BBSRC [BB/E009417/1] Funding Source: UKRI
- MRC [G120/768, G108/574] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E009417/1] Funding Source: researchfish
- Medical Research Council [G120/768, G9818340B, G108/574] Funding Source: researchfish
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.
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