7S8I

PHOSPHOPEPTIDE-SPECIFIC LC13 TCR, MONOCLINIC CRYSTAL FORM

Summary for 7S8I

• Entry DOI: 10.2210/pdb7s8i/pdb
• Descriptor: TRAV27_LC13 TCR ALPHA CHAIN, TRBV27_LC13 TCR BETA CHAIN, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: hla, mll peptide, hla-b*07:02, hla-b7, immunity, immune system, phosphopeptide, cancer, neoantigen, tcr
• Biological source: Homo sapiens (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 50331.62

Authors

Patskovsky, Y.,Nyovanie, S.,Patskovska, L.,Natarajan, A.,Joshi, B.,Morin, B.,Brittsan, C.,Huber, O.,Gordon, S.,Michelet, X.,Schmitzberger, F.,Stein, R.,Findeis, M.,Hurwitz, A.,Van Dijk, M.,Buell, J.,Underwood, D.,Krogsgaard, M. (deposition date: 2021-09-17, release date: 2022-11-02, Last modification date: 2024-11-06)

Primary citation

Patskovsky, Y.,Natarajan, A.,Patskovska, L.,Nyovanie, S.,Joshi, B.,Morin, B.,Brittsan, C.,Huber, O.,Gordon, S.,Michelet, X.,Schmitzberger, F.,Stein, R.B.,Findeis, M.A.,Hurwitz, A.,Van Dijk, M.,Chantzoura, E.,Yague, A.S.,Pollack Smith, D.,Buell, J.S.,Underwood, D.,Krogsgaard, M.
Molecular mechanism of phosphopeptide neoantigen immunogenicity.
Nat Commun, 14:3763-3763, 2023

PubMed Abstract: Altered protein phosphorylation in cancer cells often leads to surface presentation of phosphopeptide neoantigens. However, their role in cancer immunogenicity remains unclear. Here we describe a mechanism by which an HLA-B*0702-specific acute myeloid leukemia phosphoneoantigen, pMLL (EPR(pS)PSHSM), is recognized by a cognate T cell receptor named TCR27, a candidate for cancer immunotherapy. We show that the replacement of phosphoserine P with serine or phosphomimetics does not affect pMHC conformation or peptide-MHC affinity but abrogates TCR27-dependent T cell activation and weakens binding between TCR27 and pMHC. Here we describe the crystal structures for TCR27 and cognate pMHC, map of the interface produced by nuclear magnetic resonance, and a ternary complex generated using information-driven protein docking. Our data show that non-covalent interactions between the epitope phosphate group and TCR27 are crucial for TCR specificity. This study supports development of new treatment options for cancer patients through target expansion and TCR optimization.

PubMed: 37353482
DOI: 10.1038/s41467-023-39425-1

Experimental method

X-RAY DIFFRACTION (1.66 Å)