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International Immunology Advance Access published online on December 16, 2005
International Immunology, 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
Received October 18, 2004
Accepted October 31, 2005

Article

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

Heather L. Zwickey 1 *, Julia J. Unternaehrer 2 *, and Ira Mellman 2 *

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

* To whom correspondence should be addressed.
Ira Mellman, E-mail: ira.mellman{at}yale.edu


  Abstract

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.

*These authors contributed equally to this work.


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