Dendritic cells (DCs) initiate and regulate immunity against foreign and self antigens. Here we identified more than 200 individual major histocompatibility complex class II–associated peptides on human DCs and found that mature DCs selectively upregulated the self peptide CLIP. CLIP cosegregated together with foreign antigenic peptides in tetraspan microdomains on the surface and localized to DC–T cell synapses. The increased representation of CLIP–major histocompatibility complex class II complexes favored polarization of autologous naive T cells toward the nonpolarized and T helper type 2 (TH2) phenotype. There was also a considerably higher TH2/TH1 ratio in H2-DM-deficient mice, which have a CLIPhi phenotype, in contrast to wild-type, CLIPlo mice. Thus, the self peptide CLIP on DCs qualifies as an endogenous regulator in priming of T helper cells by antagonizing the polarization toward the TH1 phenotype.
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We thank C. Lallouet and N. Platania for expert technical assistance; B. Bohrmann and K. Oroszlan-Szovik (Roche Pharmaceuticals, Basel, Switzerland) for help with confocal microscopy; D. Nguyen and H. Klueter (Instituto for Transfusionmedicine and Immunology, Mannheim, Germany) for HLA-typed blood samples; and C. Benoist, D. Mathis and R. Obst (Harvard Medical School, Boston, Massachusetts) for providing H2-DM-deficient mice. The Basel Institute was founded and supported by F. Hoffmann-La Roche (Basel, Switzerland).
The authors declare no competing financial interests.
CLIP is a constituent of synapses formed between DCs and autologous T cells. (PDF 1529 kb)
Exogenous IL-12 reverts the antagonistic effect of CLIP on TH1 polarization. (PDF 48 kb)
Specificity of polycloncal rabbit IgG α-CLIP. (PDF 171 kb)
Capacity to load HLA-DR with exogenous antigen upon maturation. (PDF 97 kb)
HLA-DR (DRB*0101/1201) associated self-peptides of DCs (PDF 75 kb)
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