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http://purl.uniprot.org/citations/26507656http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26507656http://www.w3.org/2000/01/rdf-schema#comment"MHC class I-restricted epitopes, which carry a tumor-specific mutation resulting in improved MHC binding affinity, are preferred T cell receptor targets in innovative adoptive T cell therapies. However, T cell therapy requires efficient generation of the selected epitope. How such mutations may affect proteasome-mediated antigen processing has so far not been studied. Therefore, we analyzed by in vitro experiments the effect on antigen processing and recognition of a T210M exchange, which previously had been introduced into the melanoma gp100209-217 tumor epitope to improve the HLA-A*02:01 binding and its immunogenicity. A quantitative analysis of the main steps of antigen processing shows that the T210M exchange affects proteasomal cleavage site usage within the mutgp100201-230 polypeptide, leading to the generation of an unique set of cleavage products. The T210M substitution qualitatively affects the proteasome-catalyzed generation of spliced and non-spliced peptides predicted to bind HLA-A or -B complexes. The T210M substitution also induces an enhanced production of the mutgp100209-217 epitope and its N-terminally extended peptides. The T210M exchange revealed no effect on ERAP1-mediated N-terminal trimming of the precursor peptides. However, mutant N-terminally extended peptides exhibited significantly increased HLA-A*02:01 binding affinity and elicited CD8(+) T cell stimulation in vitro similar to the wtgp100209-217 epitope. Thus, our experiments demonstrate that amino acid exchanges within an epitope can result in the generation of an altered peptide pool with new antigenic peptides and in a wider CD8(+) T cell response also towards N-terminally extended versions of the minimal epitope."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m115.695189"xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/author"Keller C."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/author"Henklein P."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/author"Sette A."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/author"Sidney J."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/author"Kloetzel P.M."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/author"Mishto M."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/author"Textoris-Taube K."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/author"Liepe J."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/pages"30417-30428"xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/title"The T210M Substitution in the HLA-a*02:01 gp100 Epitope Strongly Affects Overall Proteasomal Cleavage Site Usage and Antigen Processing."xsd:string
http://purl.uniprot.org/citations/26507656http://purl.uniprot.org/core/volume"290"xsd:string
http://purl.uniprot.org/citations/26507656http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26507656
http://purl.uniprot.org/citations/26507656http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26507656
http://purl.uniprot.org/uniprot/#_A0A0A7C543-mappedCitation-26507656http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26507656
http://purl.uniprot.org/uniprot/#_A0A0A7C548-mappedCitation-26507656http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26507656
http://purl.uniprot.org/uniprot/#_A0A0A7C551-mappedCitation-26507656http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26507656
http://purl.uniprot.org/uniprot/#_A0A0G2R0N3-mappedCitation-26507656http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26507656
http://purl.uniprot.org/uniprot/#_A0A0G2R0N4-mappedCitation-26507656http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26507656
http://purl.uniprot.org/uniprot/#_A0A076JXB7-mappedCitation-26507656http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26507656
http://purl.uniprot.org/uniprot/#_A0A076L0P9-mappedCitation-26507656http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26507656