Dataset Information

Direct quantification of viral epitope abundance reveals the importance of direct and cross-presentation in driving CTL responses during influenza infection

ABSTRACT: The magnitude of CD8+ T lymphocyte (CTL) responses to infection is a function of the available naïve T cell repertoire, combined with the context and duration of antigen presentation. Whilst T cell repertoires are relatively easily studied, the context and abundance of epitopes presented on infected cells and dendritic cells (DCs) and their subsequent impact on CTL responses are generally poorly understood. Using quantitative mass spectrometry, we identified and quantified the abundance of 21 class 1 Major Histocompatibility Complex molecule (MHCI)-restricted influenza A virus (IAV)-derived peptides following either direct presentation or cross-presentation. All identified peptides, including seven novel epitopes, elicited T cell responses in infected C57BL/6 mice. Quantitation of IAV epitopes displayed via direct presentation showed a maintenance of relative epitope abundance across distinct cell types, reflecting common antigen processing mechanisms. Comparison of epitope levels displayed via direct presentation and cross-presentation revealed a broad range of directly presented epitope abundances, which was normalised during cross-presentation. Further, we observed a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drove optimal nucleoprotein (NP)366-374 presentation, while cross-presentation was optimal for acid polymerase (PA)224-233 presentation. This study provides a detailed dissection of viral pMHCI abundance after infection and reveals the importance of both direct and cross-presentation in driving dominant CTL responses. The study also demonstrates how empirical assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Dendritic Cell, Cell Culture

DISEASE(S): Influenza

SUBMITTER: Nathan Croft

LAB HEAD: Anthony Purcell

PROVIDER: PXD012728 | Pride | 2019-07-02

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20130524_Ting_P815-IAV-A10.wiff	Wiff
	20130524_Ting_P815-IAV-A10.wiff.scan	Wiff
	20130524_Ting_P815-IAV-A11.wiff	Wiff
	20130524_Ting_P815-IAV-A11.wiff.scan	Wiff
	20130524_Ting_P815-IAV-A12.wiff	Wiff

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Publications

Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses.

Wu Ting T Guan Jing J Handel Andreas A Tscharke David C DC Sidney John J Sette Alessandro A Wakim Linda M LM Sng Xavier Y X XYX Thomas Paul G PG Croft Nathan P NP Purcell Anthony W AW La Gruta Nicole L NL

Nature communications 20190628 1

The magnitude of T cell responses to infection is a function of the naïve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell ...[more]

PMID: 31253788

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