CD36 or alphavbeta3 and alphavbeta5 integrins are not essential for MHC class I cross-presentation of cell-associated antigen by CD8 alpha+ murine dendritic cells.
Cross-presentation of cell-associated Ag is thought to involve receptor-mediated uptake of apoptotic cells by dendritic cells (DC), and studies with human DC strongly implicate the endocytic receptor CD36 and the integrins alpha(v)beta(3) and/or alpha(v)beta(5) in this process. In the mouse, cross-presentation was recently shown to be a function of CD8alpha(+) DC. Here we report that CD36 is expressed on CD8alpha(+), but not on CD8alpha(-), DC. To address the role of CD36 in cross-presentation we compared CD36(-/-) and CD36(+/+) H-2(b) DC for their ability to stimulate naive OT-1 T cells specific for OVA plus H-2K(b) in the presence of OVA-loaded MHC-mismatched splenocytes as a source of cell-associated Ag for cross-presentation. Surprisingly, no difference was seen between CD36(-/-) and CD36(+/+) CD8alpha(+) DC in their ability to cross-present cell-associated OVA or to capture OVA-bearing cells. Furthermore, the proliferation of CFSE-labeled OT-1 cells in response to OVA cross-presentation in vivo was normal in CD36(-/-) bone marrow chimeras, also arguing against a necessary role for CD36 in cross-presentation by DC or other APC. DC doubly deficient for beta(3) and beta(5) integrins were similarly unimpaired in their ability to cross-present OVA-bearing cells in vitro. These data demonstrate that in the mouse, receptors other than CD36 or beta(3) and beta(5) integrins can support the specialized cross-presenting function of CD8alpha(+) DC.
Schulz
Oliver
O
Immunobiology Laboratory, Lymphocyte Molecular Biology Laboratory, and Cell Adhesion and Disease Laboratory, Cancer Research UK, London Research Institute, London, United Kingdom.
Pennington
Daniel J
DJ
Hodivala-Dilke
Kairbaan
K
Febbraio
Maria
M
Reis e Sousa
Caetano
C
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016827:CD8 Antigens / Q000096:biosynthesis*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D005260:Female; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D007275:Injections, Intravenous; D016023:Integrins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments; D019030:Receptors, Vitronectin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D018955:CD36 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; D004527:Egg Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D016023:Integrins; C110366:OVA-8; D010446:Peptide Fragments; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D010047:Ovalbumin