PDBsum entry 6o4z

Immune system

PDB id: 6o4z

Contents

Protein chains

274 a.a.

99 a.a.

Ligands

LYS-LEU-VAL-VAL-VAL-ALA-VAL-GLY-VAL

GOL ×3

SO4

Metals

_NA ×6

Waters ×252

PDB id:

6o4z

Name:

Immune system

Title:

Structure of hla-a2:01 with peptide mm92

Structure:

Mhc class i antigen. Chain: a. Engineered: yes. Beta-2-microglobulin. Chain: b. Engineered: yes. Mm92. Chain: c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-a. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Actinomyces radingae.

Resolution:

1.50Å R-factor: 0.175 R-free: 0.193

Authors:

G.Ying,A.Bitra,D.M.Zajonc

Key ref:

M.Mishto et al. (2019). An in silico-in vitro Pipeline Identifying an HLA-A^*02:01⁺ KRAS G12V⁺ Spliced Epitope Candidate for a Broad Tumor-Immune Response in Cancer Patients. Front Immunol, 10, 2572. PubMed id: 31803176 DOI: 10.3389/fimmu.2019.02572

Date:

01-Mar-19 Release date: 15-Jan-20

Protein chain

A0A140T913  (A0A140T913_HUMAN) -  Major histocompatibility complex, class I, A from Homo sapiens

Seq: 371 a.a.

Struc: 274 a.a.

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 99 a.a.

DOI no: 10.3389/fimmu.2019.02572

Front Immunol 10:2572 (2019)

PubMed id: 31803176

An in silico-in vitro Pipeline Identifying an HLA-A^*02:01⁺ KRAS G12V⁺ Spliced Epitope Candidate for a Broad Tumor-Immune Response in Cancer Patients.

M.Mishto, A.Mansurkhodzhaev, G.Ying, A.Bitra, R.A.Cordfunke, S.Henze, D.Paul, J.Sidney, H.Urlaub, J.Neefjes, A.Sette, D.M.Zajonc, J.Liepe.

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-A^*02:01 complexes.