HLAII peptide presentation of infliximab increases when complexed with TNF

Casasola-LaMacchia, A.; Seward, Robert J.; Tourdot, Sophie; Willetts, Matthew; Kruppa, Gary; Agostino, Michael; Bergeron, Gabrielle; Ahyi-Amendah, Nathalie; Ciarla, Andrew; Lu, Zhaojiang; Kim, Hai‐Young; Hickling, Timothy P.; Neubert, Hendrik

doi:10.3389/fimmu.2022.932252

Cited by 7 publications

(4 citation statements)

References 68 publications

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“…As HLA-II peptides are longer than HLA-I peptides and present with higher charge states more similar to tryptic peptides (i.e. +2 to +5), we used a previously published method based on default tryptic acquisition methods on the SCP with standard polygon filter, CE 20 eV at 1/K0 = 0.6 Vs cm−2 to 59 eV at 1/K0 = 1.6 Vs cm −2 and target intensity threshold of 20,000 (21). We observed a 2-3 fold increase of HLA-II peptide identifications on the SCP compared to the Exploris + FAIMS (Figure 2D).…”

Section: Resultsmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted March 12, 2023. ; https://doi.org/10.1101/2023.03.10.532106 doi: bioRxiv preprint acquisition methods on the SCP with standard polygon filter, CE 20 eV at 1/K0 = 0.6 Vs cm−2 to 59 eV at 1/K0 = 1.6 Vs cm −2 and target intensity threshold of 20,000 (21). We observed a 2-3 fold increase of HLA-II peptide identifications on the SCP compared to the Exploris + FAIMS (Figure 2D).…”

Section: Improved Coverage Of Hla-i and Hla-ii Immunopeptidomes On Th...mentioning

confidence: 99%

“…Here we comparatively evaluate single-shot methods on the Thermo Scientific Orbitrap Exploris 480 with FAIMS Pro (Exploris + FAIMS) and the Bruker timsTOF SCP (SCP) mass spectrometers. Acquisition methods for the SCP were optimized and evaluated for the analysis of both HLA-I and HLA-II peptides capitalizing on trapped ion-mobility mass spectrometry (TIMS) separation and parallel accumulation-serial fragmentation (PASEF) (20)(21)(22). We found that use of the SCP, a dedicated low-input instrument, improved depth of HLA-I and HLA-II immunopeptidomes >2 fold while increasing throughput nearly 4-fold relative to offline brp fractionation.…”

Section: Introductionmentioning

confidence: 99%

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Sensitive, high-throughput HLA-I and HLA-II immunopeptidomics using parallel accumulation-serial fragmentation mass spectrometry

Phulphagar¹,

Ctortecka²,

Vaca³

et al. 2023

Preprint

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Comprehensive, in-depth identification of the human leukocyte antigen HLA-I and HLA-II tumor immunopeptidome can inform the development of cancer immunotherapies. Mass spectrometry (MS) is powerful technology for direct identification of HLA peptides from patient derived tumor samples or cell lines. However, achieving sufficient coverage to detect rare, clinically relevant antigens requires highly sensitive MS-based acquisition methods and large amounts of sample. While immunopeptidome depth can be increased by off-line fractionation prior to MS, its use is impractical when analyzing limited amounts of primary tissue biopsies. To address this challenge, we developed and applied a high throughput, sensitive, single-shot MS-based immunopeptidomics workflow that leverages trapped ion mobility time-of-flight mass spectrometry on the Bruker timsTOF SCP. We demonstrate >2-fold improved coverage of HLA immunopeptidomes relative to prior methods with up to 15,000 distinct HLA-I and HLA-II peptides from 4e7 cells. Our optimized single-shot MS acquisition method on the timsTOF SCP maintains high coverage, eliminates the need for off-line fractionation and reduces input requirements to as few as 1e6 A375 cells for > 800 distinct HLA-I peptides. This depth is sufficient to identify HLA-I peptides derived from cancer-testis antigen, and novel/unannotated open reading frames. We also apply our optimized single-shot SCP acquisition methods to tumor derived samples, enabling sensitive, high throughput and reproducible immunopeptidome profiling with detection of clinically relevant peptides from less than 4e7 cells or 15 mg wet weight tissue.

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Section: Resultsmentioning

confidence: 99%

Section: Improved Coverage Of Hla-i and Hla-ii Immunopeptidomes On Th...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sensitive, high-throughput HLA-I and HLA-II immunopeptidomics using parallel accumulation-serial fragmentation mass spectrometry

Phulphagar¹,

Ctortecka²,

Vaca³

et al. 2023

Preprint

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“…Therefore, a better investigation of MHC-presented peptides derived from biotherapeutics is a fundamental part of the study of immunogenicity risk assessment of the drug. The peptides presented by APCs varies depending on both the enzymes that the protein encounter on their pathways and on the receptivity of MHC II, however, in recent years, different factors that may affect epitope presentation have been studied [27].…”

Section: Peptide Recognition In T-cell Mediated Immunogenicitymentioning

confidence: 99%

Therapeutic proteins immunogenicity: a peptide point of view

Real-Fernandez,

Errante,

Di Santo

et al. 2023

Explor Drug Sci

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Protein therapeutics are extensively used in the treatment of autoimmune diseases, but a subset of patients appears to be refractory to these treatments, mainly due to the development of an immune response to the drug. A better understanding of the mechanism underlying the therapeutic drug’s failure becomes fundamental for the development of new and more effective treatments. Unfortunately, there are few cases where the exact mechanisms through which drugs bypass immunological tolerance and provoke immunogenicity have been studied. In this context, peptide epitope identification gained increasing importance in investigating the molecular mechanism of therapeutic drug’s immune responses. Despite peptide identification and use to monitor anti-drug antibody (ADA) profiles is a promising research field, their use is far away from a wide application both at the research and at the commercial level. Herein it is reported a compilation of studies in which peptides are directly involved in anti-drug immune responses, becoming the molecular key step for a better understanding of refractory reactions in therapeutic drugs. An overview on T-cell and B-cell peptide recognition is given, showing the growing potential and advantages of peptides when used in the field of refractoriness to drugs. This review includes studies describing antigenic peptides that enable enhanced ADA detection directly in patients’ sera, as well as the proof of concept that asses the use of peptides instead of proteins, to facilitate the identification of neutralizing ADA.

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