Crucial Parameters for Immunopeptidome Characterization: A Systematic Evaluation

Immunopeptidomics is the area of knowledge focused on the study of peptides assembled in the major histocompatibility complex (MHC), or human leukocyte antigen (HLA) in humans, which could activate the immune response via specific and selective T cell recognition. Advances in high-sensitivity mass s...

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Detalles Bibliográficos
Autores: Juanes-Velasco, Pablo, Arias-Hidalgo, Carlota, García-Vaquero, Marina L., Sotolongo-Ravelo, Janet, Paíno, Teresa, Lécrevisse, Quentin, Landeira-Viñuela, Alicia, Góngora, Rafael, Hernández, Ángela-Patricia, Fuentes, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/380697
Acceso en línea:http://hdl.handle.net/10261/380697
Access Level:acceso abierto
Palabra clave:Immunopeptidomics
Immunopeptidome
HLA
MHC
LC-MS/MS
Descripción
Sumario:Immunopeptidomics is the area of knowledge focused on the study of peptides assembled in the major histocompatibility complex (MHC), or human leukocyte antigen (HLA) in humans, which could activate the immune response via specific and selective T cell recognition. Advances in high-sensitivity mass spectrometry have enabled the detailed identification and quantification of the immunopeptidome, significantly impacting fields like oncology, infections, and autoimmune diseases. Current immunopeptidomics approaches primarily focus on workflows to identify immunopeptides from HLA molecules, requiring the isolation of the HLA from relevant cells or tissues. Common critical steps in these workflows, such as cell lysis, HLA immunoenrichment, and peptide isolation, significantly influence outcomes. A systematic evaluation of these steps led to the creation of an ‘Immunopeptidome Score’ to enhance the reproducibility and robustness of these workflows. This score, derived from LC-MS/MS datasets (ProteomeXchange identifier PXD038165), in combination with available information from public databases, aids in optimizing the immunopeptidome characterization process. The ‘Immunopeptidome Score’ has been applied in a systematic analysis of protein extraction, HLA immunoprecipitation, and peptide recovery yields across several tumor cell lines enabling the selection of peptides with optimal features and, therefore, the identification of potential biomarker and therapeutic targets.