scholarly journals Sensitive and quantitative detection of MHC-I displayed neoepitopes using a semi-automated workflow and TOMAHAQ mass spectrometry

2021 ◽  
pp. 100108
Author(s):  
Samuel B. Pollock ◽  
Christopher M. Rose ◽  
Martine Darwish ◽  
Romain Bouziat ◽  
Lélia Delamarre ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Quantitative Detection ◽  
Mhc I

scholarly journals Sensitive and quantitative detection of MHC-I displayed neoepitopes using a semi-automated workflow and TOMAHAQ mass spectrometry

2020 ◽  
Author(s):  
Samuel B. Pollock ◽  
Christopher M. Rose ◽  
Martine Darwish ◽  
Romain Bouziat ◽  
Lélia Delamarre ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Sensitivity ◽  
Cell Receptor ◽  
Quantitative Detection ◽  
Mhc I ◽  
Mass Spectrometry Technique ◽  
Spectrometry Technique ◽  
Receptor Targets ◽  
Multiple Conditions

AbstractAdvances in several key technologies, including MHC peptidomics, has helped fuel our understanding of basic immune regulatory mechanisms and identify T cell receptor targets for the development of immunotherapeutics. Isolating and accurately quantifying MHC-bound peptides from cells and tissues enables characterization of dynamic changes in the ligandome due to cellular perturbations. This multi-step analytical process remains challenging, and throughput and reproducibility are paramount for rapidly characterizing multiple conditions in parallel. Here, we describe a robust and quantitative method whereby peptides derived from MHC-I complexes from a variety of cell lines, including challenging adherent lines, can be enriched in a semi-automated fashion on reusable, dry-storage, customized antibody cartridges. TOMAHAQ, a targeted mass spectrometry technique that combines sample multiplexing and high sensitivity, was employed to characterize neoepitopes displayed on MHC-I by tumor cells and to quantitatively assess the influence of neoantigen expression and induced degradation on neoepitope presentation.

Quantitative detection of amyloid-β peptides by mass spectrometry: state of the art and clinical applications

2015 ◽  
Vol 53 (10) ◽  
Author(s):  
Pauline Bros ◽  
Vincent Delatour ◽  
Jérôme Vialaret ◽  
Béatrice Lalere ◽  
Nicolas Barthelemy ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Amyloid Β ◽  
Clinical Applications ◽  
Health Concern ◽  
Quantitative Detection ◽  
Csf Biomarkers ◽  
Aβ Peptides ◽  
The Past ◽  
Analytical Phase ◽  
Interesting Alternative

AbstractAlzheimer’s disease (AD) is the most common form of dementia in humans, and a major public health concern with 35 million of patients worldwide. Cerebrospinal fluid (CSF) biomarkers being early diagnostic indicators of AD, it is essential to use the most efficient analytical methods to detect and quantify them accurately. These biomarkers, and more specifically amyloid-β (Aβ) peptides, are measured in routine clinical practice using immunoassays. However, there are several limits to this immunodetection in terms of specificity and multiplexing of the multiple isoforms of the Aβ peptides. To overcome these issues, the quantification of these analytes by mass spectrometry (MS) represents an interesting alternative, and several assays have been described over the past years. This article reviews the different Aβ peptides quantitative MS-based approaches published so far, compares their pre-analytical phase, and the different quantitative strategies implemented that might be suitable for clinical applications.

scholarly journals MHC-I Ligand Discovery Using Targeted Database Searches of Mass Spectrometry Data: Implications for T-Cell Immunotherapies

2017 ◽  
Vol 16 (4) ◽  
pp. 1806-1816 ◽  
Author(s):  
J. Patrick Murphy ◽  
Prathyusha Konda ◽  
Daniel J. Kowalewski ◽  
Heiko Schuster ◽  
Derek Clements ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
T Cell ◽  
Mass Spectrometry Data ◽  
Mhc I ◽  
Ligand Discovery

scholarly journals ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer

2020 ◽  
Author(s):  
Juan L. Trincado ◽  
Marina Reixachs-Sole ◽  
Judith Pérez-Granado ◽  
Tim Fugmann ◽  
Ferran Sanz ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Immune Escape ◽  
Positive Response ◽  
Immune Checkpoint Blockade ◽  
Normal Cells ◽  
Mhc I ◽  
Molecular Determinants ◽  
Associated Proteins ◽  
Melanoma Patients ◽  
Associated Mass

AbstractImmunotherapies provide effective treatments for previously untreatable tumors, but the molecular determinants of response remain to be elucidated. Here, we describe a pipeline, ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer), for the comprehensive identification of cancer-specific splicing-derived epitopes. Using RNA sequencing and mass spectrometry for MHC-I associated proteins, ISOTOPE identified neoepitopes from cancer-specific splicing event types that are potentially presented by MHC-I complexes. We found that, in general, cancer-specific splicing alterations led more frequently to the depletion of potential self-antigens compared to the generation of neoepitopes. The potential loss of native epitopes was validated using MHC-I associated mass spectrometry from normal cells. Furthermore, analysis of two cohorts of melanoma patients with ISOTOPE identified that splicing-derived neoepitopes with higher MHC-I binding affinity associate with positive response to immune checkpoint blockade therapy. Additionally, we found a more frequent depletion of native epitopes in non-responders, suggesting a new mechanism of immune escape. Our analyses highlight the diversity of the immunogenic impacts of cancer-specific splicing alterations and the importance of studying splicing alterations to fully characterize the determinants of response to immunotherapies. ISOTOPE is available at https://github.com/comprna/ISOTOPE

Sign in / Sign up

Export Citation Format

Share Document