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International Immunology Advance Access originally published online on December 16, 2005
International Immunology 2006 18(1):199-209; doi:10.1093/intimm/dxh363
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Presentation of self-antigens on MHC class II molecules during dendritic cell maturation

Heather L. Zwickey1,*, Julia J. Unternaehrer2,* and Ira Mellman2

1 Helfgott Research Institute, National College of Naturopathic Medicine, 049 SW Porter Street, Portland, OR 97201, USA
2 Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, PO Box 208002, New Haven, CT 06520, USA

Correspondence to: I. Mellman; E-mail: ira.mellman{at}yale.edu

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.

Keywords: antigen competition, antigen presentation, CD4 T cells, co-stimulation, dendritic cells, HEL, self-antigen, tolerance

Transmitting editor: K. Inaba

* These authors contributed equally to this work.


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