6O4Z

Structure of HLA-A2:01 with peptide MM92

Summary for 6O4Z

• Entry DOI: 10.2210/pdb6o4z/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, MM92, ... (7 entities in total)
• Functional Keywords: mhc class 1 molecule, antigen presentation, peptide interaction; peptide complex, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 44867.67

Authors

Ying, G.,Bitra, A.,Zajonc, D.M. (deposition date: 2019-03-01, release date: 2020-01-15, Last modification date: 2024-10-09)

Primary citation

Mishto, M.,Mansurkhodzhaev, A.,Ying, G.,Bitra, A.,Cordfunke, R.A.,Henze, S.,Paul, D.,Sidney, J.,Urlaub, H.,Neefjes, J.,Sette, A.,Zajonc, D.M.,Liepe, J.
Anin silico-in vitroPipeline Identifying an HLA-A*02:01+KRAS G12V+Spliced Epitope Candidate for a Broad Tumor-Immune Response in Cancer Patients.
Front Immunol, 10:2572-2572, 2019

PubMed Abstract: Targeting CD8 T cells to recurrent tumor-specific mutations can profoundly contribute to cancer treatment. Some of these mutations are potential tumor antigens although they can be displayed by non-spliced epitopes only in a few patients, because of the low affinity of the mutated non-spliced peptides for the predominant HLA class I alleles. Here, we describe a pipeline that uses the large sequence variety of proteasome-generated spliced peptides and identifies spliced epitope candidates, which carry the mutations and bind the predominant HLA-I alleles with high affinity. They could be used in adoptive T cell therapy and other anti-cancer immunotherapies for large cohorts of cancer patients. As a proof of principle, the application of this pipeline led to the identification of a KRAS G12V mutation-carrying spliced epitope candidate, which is produced by proteasomes, transported by TAPs and efficiently presented by the most prevalent HLA class I molecules, HLA-A02:01 complexes.

PubMed: 31803176
DOI: 10.3389/fimmu.2019.02572

Experimental method

X-RAY DIFFRACTION (1.5 Å)