Upregulation of the CLIP self peptide on mature dendritic cells antagonizes T helper type 1 polarization.
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 (T(H)2) phenotype. There was also a considerably higher T(H)2/T(H)1 ratio in H2-DM-deficient mice, which have a CLIP(hi) phenotype, in contrast to wild-type, CLIP(lo) 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 T(H)1 phenotype.
Röhn
Till A
TA
Basel Institute for Immunology, Basel, Switzerland.
Boes
Marianne
M
Wolters
Dirk
D
Spindeldreher
Sebastian
S
Müller
Bernd
B
Langen
Hanno
H
Ploegh
Hidde
H
Vogt
Anne B
AB
Kropshofer
Harald
H
D017951:Antigen Presentation / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D002853:Chromatography, Liquid; D003713:Dendritic Cells / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D008213:Lymphocyte Activation / Q000276:immunology*; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D011940:Receptor Aggregation / Q000276:immunology*; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018417:Th1 Cells / Q000276:immunology*; D015854:Up-Regulation
D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain