Poster Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

Expression of the chemokine receptor XCR1 characterizes the cross-presenting lineage of dendritic cells in mouse and men (#284)

Annabell Bachem 1 2 , Evelyn Hartung 1 , Steffen Güttler 1 3 , Martina Becker 1 , Ahmed Mora 1 4 , Xuefei Zhou 1 5 , Anika Hegemann 1 , Maud Platinga 6 , Eliza Mazzini 7 , Patrizia Stoitzner 8 , Stephanie Gurka 1 , Volker Henn 1 , Hans W. Mages 1 , Richard A. Kroczek 1
  1. Robert Koch Institute, Berlin, Germany
  2. present adress: Bedoui Laboratory, Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunology, The University of Melbourne, Melbourne, Australia
  3. present adress: Taconic, Cologne, Germany
  4. present adress: Chemistry Department, Al-Azhar University, Cairo, Egypt
  5. present adress: Hexal, Holzkirchen, Germany
  6. Laboratory of Immunoregulation and Mucosal Immunology, Department of Respiratory Diseases, University Hospital of Ghent, Ghent, Belgium
  7. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
  8. Department of Dermatology and Venereology, University of Innsbruck, Innsbruck, Austria
Cross-presentation by dendritic cells (DC) is a process in which extracellular antigen is shunted into the MHC I presentation pathway and presented to CD8+ T cells. Due to the lack of an appropriate lineage marker, murine cross-presenting DC were to date defined by the expression of the co-receptor CD8 in the spleen and the integrin CD103 in the periphery. In humans, the scarcity of DC and in particular the very low frequency of CD141+ (BDCA-3) DC in the peripheral blood, impeded their functional characterization and complicated their comparison to primary murine DC subsets. Using a newly generated monoclonal antibody specific for the chemokine receptor XCR1, we determined that 80% of CD8+ DC and 5% of CD8- DC in the spleen uniquely express XCR1 on their surface. These XCR1+ DC efficiently take up cellular material and excel in antigen cross-presentation, independent of their CD8 expression. In lymph nodes and peripheral tissues, XCR1+ DC largely, but not fully, correspond to CD103+ DC. Furthermore, we demonstrate that XCR1+ DC in the spleen, lymph nodes, and peripheral tissues are dependent on the growth factor Flt3 ligand and are selectively absent in animals deficient for the transcription factors Batf3 and Irf-8. Therefore, XCR1 emerges as the first highly specific surface marker of cross-presenting Batf3- and Irf-8-dependent DC in the mouse. Crucial for the translation of mouse models to the human, we additionally demonstrate that XCR1 is specifically expressed on human primary CD141+ DC. This DC subset, similar to murine XCR1+ DC, excels in cross-presentation of soluble and cell-associated antigens. Hence, the expression of XCR1 demarcates a subset of human and mouse DC that are functional homologues. At the same time, XCR1 emerges as a highly attractive structure for targeting of antigen and induction of CD8 T cell cytotoxic immunity in prophylactic or therapeutic vaccines.