Dendritic cells (DC) are unique in their capacity to induce and regulate immune responses. Their special abilities in pathogen detection, antigen processing and presentation, and communication to T cells are determined by plasma membrane and endosomal proteins. Our knowledge of DC biology is mainly based on studies of in vitro generated-DC, which are not representative of those found in vivo. Clear evidence from the laboratories of Heath, Shortman and Villadangos show that different subtypes of DC show radical differences in antigen handling, T cell activation, and roles in immunity and tolerance.The goal of this project is to compare in depth the protein composition of different DC subtypes as they occur in vivo. We propose to use a proteomic approach to analyse plasma membrane and endosomal proteins from two major DC subtypes: CD4 DC and CD8 DC, in a resting or activated state. The most interesting molecules discovered by the proteomic analysis will be further analysed in functional studies. This project will reveal differentially expressed membrane and endosomal proteins, which could be used to target distinct DC subsets as a strategy to improve vaccination or suppress autoimmunity.The proteomic description of DC diversity we will obtain will be beneficial for the wider scientific community. The feasibility of the project is founded on the expertise and resources available to the scientists involved both at the Immunology Division, Walter and Eliza Hall Institute (Melbourne, Australia) and INSERM U653, Institut Curie (Paris, France), all of which have a demonstrated track record in their respective areas. This proposal will create the opportunity for cooperation between French and third country research institutions and allow transfer of research competencies while reinforcing the international dimension of the career of the fellow.