Cross-presentation of cell-associated antigens by CD8alpha+ dendritic cells is attributable to their ability to internalize dead cells.
In the mouse, cross-presentation is an exclusive property of the CD8alpha+ subset of dendritic cells (DC) but the basis for this selectivity remains unclear. Here we report that splenic CD8alpha+ DC are much superior to other DC subsets in internalizing dying cells in vitro. In contrast, CD8alpha+, CD8alpha- CD4+ and CD8alpha- CD4- DC subsets phagocytose bacteria or latex beads to a similar extent. Although CD8alpha+ DC are better than CD4+ DC at presenting ovalbumin (OVA)-loaded splenocytes to naïve OT-I T lymphocytes, CD4+ DC are better at presenting OVA-expressing Escherichia coli to the same T cells. In both cases, presentation is abrogated by lactacystin. These results show that both splenic CD8alpha+ and CD8alpha- DC can present exogenous antigens on major histocompatibility complex (MHC) class I via a proteasome-dependent pathway and suggest that the specialized cross-presenting function of CD8alpha+ DC is a result of their ability to endocytose dying cells rather than a unique pathway for handling endosomal contents.
Schulz
Oliver
O
Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Reis e Sousa
Caetano
C
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis*; D018929:Cell Culture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D010047:Ovalbumin / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*
D000942:Antigens, Bacterial; D015704:CD4 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; D010047:Ovalbumin