MS-Based HLA-II Peptidomics Combined With Multiomics Will Aid the Development of Future Immunotherapies

Taylor, Hannah B; Klaeger, Susan; Clauser, Karl R.; Sarkizova, Siranush; Weingarten-Gabbay, Shira; Graham, Daniel B.; Carr, Steven A.; Abelin, Jennifer G.

doi:10.1016/j.mcpro.2021.100116

Cited by 17 publications

(20 citation statements)

References 145 publications

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“…As expected, the deconvoluted motifs matched more to HLA-DR heterodimers, and less so to HLA-DP and HLA-DQ heterodimers, in both cell lines, as HLA-DR is often expressed at higher levels when compared to HLA-DP and HLA-DQ. 55 Notably, some of the HLA-II alleles expressed by the two cell lines and confirmed by motif deconvolution are highly prevalent in the European (EUR) and US populations, including DRB1*07:01 (~14% EUR, ~12% US), expressed by A549 and DRB1*15:01 (~14% EUR, ~11% US), and DRB5*01:01 (~16% EUR), expressed by HEK293T ( Table S1A ).…”

Section: Resultsmentioning

confidence: 90%

The HLA-II immunopeptidome of SARS-CoV-2

Weingarten-Gabbay,

Chen,

Sarkizova

et al. 2024

Cell Reports

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Section: Resultsmentioning

confidence: 90%

The HLA-II immunopeptidome of SARS-CoV-2

Weingarten-Gabbay,

Chen,

Sarkizova

et al. 2024

Cell Reports

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“…Due to these expression patterns and the well documented cytotoxic activity of CD8+ T cells, HLA-I tumor immunopeptidomes are most frequently studied (1,5,8). Nonetheless, both HLA-I and HLA-II tumor antigen profiling are needed, as the latter play an important role in anti-tumor immunity in both HLA-II and non-HLA-II expressing tumors (9)(10)(11).…”

Section: Abbreviationsmentioning

confidence: 99%

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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“…These endosomes and phagosomes are able to fuse with the MHC II compartment (MIIC) in the cytosol [ 28 ]. The MIIC is rich in various enzymes and acidic milieu that account for the degradation of exogenous antigens into short peptides consisting of 13–18 amino acids [ 57 ]. These short peptides bind to MHC II and form stable peptide-MHC II complexes, which are then transported to the cell surface.…”

Section: Antigen Presentation Of Mhc Moleculesmentioning

confidence: 99%

Molecular Characteristics, Functional Definitions, and Regulatory Mechanisms for Cross-Presentation Mediated by the Major Histocompatibility Complex: A Comprehensive Review

Liu,

Wei,

Sun

et al. 2023

IJMS

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The major histocompatibility complexes of vertebrates play a key role in the immune response. Antigen-presenting cells are loaded on MHC I molecules, which mainly present endogenous antigens; when MHC I presents exogenous antigens, this is called cross-presentation. The discovery of cross-presentation provides an important theoretical basis for the study of exogenous antigens. Cross-presentation is a complex process in which MHC I molecules present antigens to the cell surface to activate CD8+ T lymphocytes. The process of cross-representation includes many components, and this article briefly outlines the origins and development of MHC molecules, gene structures, functions, and their classical presentation pathways. The cross-presentation pathways of MHC I molecules, the cell lines that support cross-presentation, and the mechanisms of MHC I molecular transporting are all reviewed. After more than 40 years of research, the specific mechanism of cross-presentation is still unclear. In this paper, we summarize cross-presentation and anticipate the research and development prospects for cross-presentation.

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MS-Based HLA-II Peptidomics Combined With Multiomics Will Aid the Development of Future Immunotherapies

Cited by 17 publications

References 145 publications

The HLA-II immunopeptidome of SARS-CoV-2

The HLA-II immunopeptidome of SARS-CoV-2

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

Molecular Characteristics, Functional Definitions, and Regulatory Mechanisms for Cross-Presentation Mediated by the Major Histocompatibility Complex: A Comprehensive Review

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