Proteomics,Multiomics

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MHC II immunopeptidome during Plasmodium berghei blood stage infection

ABSTRACT: In malaria, T cells play a dual role by both restricting parasite growth and mediating immunopathology such as the deadly neuroinflammation called cerebral malaria. During experimental cerebral malaria (ECM), IFN produced by CD4 T cells promotes CD8 T cell sequestration in brain capillaries, resulting in endothelial damage, oedema and death. However the antigen-presenting cells controlling the development of CD4 T cell responses, as well as the antigens recognized by these CD4 T cells, are unknown. Here we used mass spectrometry to characterize the MHC II immunopeptidome presented by dendritic cells during blood stage malaria in C57BL/6 mice. We identified 14 MHC II ligands derived from 13 conserved Plasmodium berghei proteins that we validated in vivo. This work profiles the first MHC II immunopeptidome in a mouse model of blood stage malaria.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Plasmodium Berghei Anka Mus Musculus (mouse)

TISSUE(S): Dendritic Cell, Blood

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: SALIOU Jean-Michel  

LAB HEAD: Jean-Michel Saliou

PROVIDER: PXD007628 | Pride | 2017-09-20

REPOSITORIES: Pride

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Profiling MHC II immunopeptidome of blood-stage malaria reveals that cDC1 control the functionality of parasite-specific CD4 T cells.

Draheim Marion M   Wlodarczyk Myriam F MF   Crozat Karine K   Saliou Jean-Michel JM   Alayi Tchilabalo Dilezitoko TD   Tomavo Stanislas S   Hassan Ali A   Salvioni Anna A   Demarta-Gatsi Claudia C   Sidney John J   Sette Alessandro A   Dalod Marc M   Berry Antoine A   Silvie Olivier O   Blanchard Nicolas N  

EMBO molecular medicine 20171101 11

In malaria, CD4 Th1 and T follicular helper (T<sub>FH</sub>) cells are important for controlling parasite growth, but Th1 cells also contribute to immunopathology. Moreover, various regulatory CD4 T-cell subsets are critical to hamper pathology. Yet the antigen-presenting cells controlling Th functionality, as well as the antigens recognized by CD4 T cells, are largely unknown. Here, we characterize the MHC II immunopeptidome presented by DC during blood-stage malaria in mice. We establish the i  ...[more]

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