Upregulation of the CLIP self peptide on mature dendritic cells antagonizes T helper type 1 polarization

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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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Figure 1: Accumulation of CLIP–MHC class II complexes on mature DCs.
Figure 2: Downregulation of HLA-DM and its activity during maturation.
Figure 3: Copresentation of CLIP and antigenic peptides.
Figure 4: CLIP-MHC II complexes cluster in the central area of the synapse formed between mature DCs and Jurkat T cells.
Figure 5: CLIP is a constituent of CDw78 microdomains of DCs and tonsil APCs.
Figure 6: CLIP on DCs influences polarization of naive CD4+ T cells.
Figure 7: Endogenous CLIP effects on T cell polarization in vivo.


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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).

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Correspondence to Harald Kropshofer.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

CLIP is a constituent of synapses formed between DCs and autologous T cells. (PDF 1529 kb)

Supplementary Fig. 2

Exogenous IL-12 reverts the antagonistic effect of CLIP on TH1 polarization. (PDF 48 kb)

Supplementary Fig. 3

Specificity of polycloncal rabbit IgG α-CLIP. (PDF 171 kb)

Supplementary Fig. 4

Capacity to load HLA-DR with exogenous antigen upon maturation. (PDF 97 kb)

Supplementary Table 1

HLA-DR (DRB*0101/1201) associated self-peptides of DCs (PDF 75 kb)

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