Presentation of self-antigens on MHC class II molecules during dendritic cell maturation.
Little is known about how dendritic cells (DCs) maintain a balance between tolerance and immunity for antigens synthesized by DCs themselves. Using transgenic DCs expressing a model self-antigen, in vitro self-peptide-MHC class II complex formation and presentation increased with DC maturation, as for exogenous antigens. In vivo, however, even 'immature' DCs isolated from steady-state lymph nodes expressed MHC at mature cell levels, although many were also CD86 low. Adoptive transfer of naive specific T cells into unstimulated transgenic mice resulted in tolerance. If the mice were also injected with anti-CD40 or Listeria monocytogenes, there was robust specific T cell expansion and inflammation. Thus, DC-endogenous antigens may induce tolerance, but only in the absence of potent maturation stimuli.
Zwickey
Heather L
HL
Helfgott Research Institute, National College of Naturopathic Medicine, 049 SW Porter Street, Portland, OR 97201, USA.
Unternaehrer
Julia J
JJ
Mellman
Ira
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D005802:Genes, MHC Class II / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D019013:CD40 Antigens; D019002:CD56 Antigen