About: A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations
Creator	Nerli, Santrupti Nguyen, Son Tripathi, Sarvind Yamaguchi, Karissa Yarmarkovich, Mark Haussler˚, David Madejska, Ada Maris, John Mcshan, Andrew Rao, Arjun Salama, Sofie Sgourakis˚, Nikolaos Toor, Jugmohit
source	Medline; PMC
abstract	The identification of recurrent human leukocyte antigen (HLA) neoepitopes driving T cell responses against tumors poses a significant bottleneck in the development of approaches for precision cancer therapeutics. Here, we employ a bioinformatics method, Prediction of T Cell Epitopes for Cancer Therapy, to analyze sequencing data from neuroblastoma patients and identify a recurrent anaplastic lymphoma kinase mutation (ALK R1275Q) that leads to two high affinity neoepitopes when expressed in complex with common HLA alleles. Analysis of the X-ray structures of the two peptides bound to HLA-B15:01 reveals drastically different conformations with measurable changes in the stability of the protein complexes, while the self-epitope is excluded from binding due to steric hindrance in the MHC groove. To evaluate the range of HLA alleles that could display the ALK neoepitopes, we used structure-based Rosetta comparative modeling calculations, which accurately predict several additional high affinity interactions and compare our results with commonly used prediction tools. Subsequent determination of the X-ray structure of an HLA-A01:01 bound neoepitope validates atomic features seen in our Rosetta models with respect to key residues relevant for MHC stability and T cell receptor recognition. Finally, MHC tetramer staining of peripheral blood mononuclear cells from HLA-matched donors shows that the two neoepitopes are recognized by CD8+ T cells. This work provides a rational approach toward high-throughput identification and further optimization of putative neoantigen/HLA targets with desired recognition features for cancer immunotherapy.
has issue date	2018-01-30(xsd:dateTime)
bibo:doi	10.3389/fimmu.2018.00099
bibo:pmid	29441070
has license	cc-by
sha1sum (hex)	f41bb5faed6594d62ba991668997e97600bf0af1
schema:url	https://doi.org/10.3389/fimmu.2018.00099
resource representing a document's title	A Recurrent Mutation in Anaplastic Lymphoma Kinase with Distinct Neoepitope Conformations
has PubMed Central identifier	PMC5797543
has PubMed identifier	29441070
schema:publication	Front Immunol
resource representing a document's body	covid:f41bb5faed6594d62ba991668997e97600bf0af1#body_text
is schema:about of	named entity 'TARGET' named entity 'SUPPLEMENTARY MATERIAL' named entity 'ENTIRE' named entity 'DISTINCT' named entity 'TARGET' named entity 'PRIMARY' named entity 'SHEET' named entity 'SPECIFIC' named entity 'ANAPLASTIC LYMPHOMA KINASE' named entity 'LIST' named entity 'MUTATION' named entity 'SAMPLE' named entity 'PREDICTED' named entity 'MUTATION' named entity 'INCLUDING' named entity 'PATIENTS' named entity 'RESULTS' named entity 'GENES' named entity 'MUTATED' named entity 'NBL' named entity 'SCORE' named entity 'BINDING' named entity 'RECURRENT' named entity 'SUPPLEMENTARY DATA' named entity 'THE TABLE' named entity 'MHC' named entity 'ITS' named entity 'genes' named entity 'binding' named entity 'Data' named entity 'neoepitopes' named entity 'allele' named entity 'molecular interactions' named entity 'decamer' named entity 'X-ray structures' named entity 'HLA-A' named entity 'decamer' named entity 'mutation' named entity 'protein' named entity 'nonamer' named entity 'X-ray structure' named entity 'HLA' named entity 'database' named entity 'mutation' named entity 'tumors' named entity 'mutation' named entity 'peptide' named entity 'X-axis' named entity 'mutation' named entity 'molecular interactions' named entity 'MHC' named entity 'amino acids' named entity 'peptide' named entity 'Somatic Mutations' named entity 'wild-type' named entity 'Y-axis' named entity 'allele' named entity 'allele' named entity 'allele' named entity 'HLA-B' named entity 'allele' named entity 'alanine' named entity 'peptide' named entity 'MHC' named entity 'mutation' named entity 'neoepitopes' named entity 'genes' named entity 'describes' named entity 'predicted'

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