Journal article

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

Ting Wu, Jing Guan, Andreas Handel, David C Tscharke, John Sidney, Alessandro Sette, Linda M Wakim, Xavier YX Sng, Paul G Thomas, Nathan P Croft, Anthony W Purcell, Nicole L La Gruta

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2019

Abstract

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 types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant ..

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University of Melbourne Researchers

Grants

Awarded by Australian Research Council (ARC)


Awarded by National Health and Medical Research Council (NHMRC) Program


Awarded by NHMRC


Awarded by NIH/NIAID


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

We thank Stephen J. Turner and Jamie Rossjohn for critical reading of the manuscript, Lukasz Kedzierski and Claerwen Jones for technical assistance, and staff at Monash University flow cytometry, biomedical proteomics and animal core facilities. We thank Dr. Ken Rock for provision of DC2.4 cells and Dr. Acha-Orbea for provision of Mutu DCs. This work was supported by a Sylvia and Charles Viertel Senior Medical Research Fellowship, an Australian Research Council (ARC) Future Fellowship FT170100174, and a National Health and Medical Research Council (NHMRC) Program grant APP1071916 (to N.L.L.G.), an NHMRC Principal Research Fellowship APP1137739 (to A.W.P.), an NHMRC Senior Research Fellowship APP1104329 (to D.C.T.) and an NHMRC Project grant APP1084283 (to A.W.P., N.P.C.,and D.C.T.). A. H.and P.G.T. were partially supported by NIH/NIAID grant U19AI117891.