Tetraspan microdomains distinct from lipid rafts enrich select peptide-MHC class II complexes.
Complexes of peptide and major histocompatibility complex (MHC) class II are expressed on the surface of antigen-presenting cells but their molecular organization is unknown. Here we show that subsets of MHC class II molecules localize to membrane microdomains together with tetraspan proteins, the peptide editor HLA-DM and the costimulator CD86. Tetraspan microdomains differ from other membrane areas such as lipid rafts, as they enrich MHC class II molecules carrying a selected set of peptide antigens. Antigen-presenting cells deficient in tetraspan microdomains have a reduced capacity to activate CD4+ T cells. Thus, the organization of uniformly loaded peptide-MHC class II complexes in tetraspan domains may be a very early event that determines both the composition of the immunological synapse and the quality of the subsequent T helper cell response.
Kropshofer
H
H
Basel Institute for Immunology, 4005 Basel, Switzerland. harald.kropshofer@roche.com
Spindeldreher
S
S
Röhn
T A
TA
Platania
N
N
Grygar
C
C
Daniel
N
N
Wölpl
A
A
Langen
H
H
Horejsi
V
V
Vogt
A B
AB
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002451:Cell Compartmentation; D002461:Cell Line, Transformed; D003505:Cyclodextrins / Q000494:pharmacology; D011992:Endosomes / Q000378:metabolism; D006681:HLA-D Antigens / Q000276:immunology*; D006682:HLA-DP Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000378:metabolism; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000276:immunology*; D021962:Membrane Microdomains / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000032:analysis; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012503:Saponins / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D047392:beta-Cyclodextrins
D000911:Antibodies, Monoclonal; D000941:Antigens; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D051940:B7-2 Antigen; C497964:CD86 protein, human; C445501:CDw78 antigen; D003505:Cyclodextrins; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D012503:Saponins; D047392:beta-Cyclodextrins; C045084:invariant chain; C031215:betadex