title: Tetraspanins CD37 and CD151 differentially regulate Ag presentation and T-cell co-stimulation by DC.
abstract: A major question in immunology is how DC can display limited amounts of individual peptide-MHC complexes and still induce cross-linking of T-cell receptors to initiate cellular responses. One suggested mechanism is that MHC exists at the cell surface in high avidity multimers, and tetraspanin proteins, known to laterally associate with both MHC classes I and II, promote MHC multimerisation. To validate this theory, we tested the ability of DC deficient in either one of two typical tetraspanin molecules: CD37 or CD151 to present peptide to Ag-specific T cells. Surprisingly, although they exhibited no developmental or maturation defects, DC lacking either CD37 or CD151 expression were hyper-stimulatory to T cells. We demonstrate that CD37 and CD151 control DC-mediated T-cell activation by two different mechanisms: CD151 regulates co-stimulation whereas CD37 regulates peptide/MHC presentation. The implications of these results on the model suggesting that tetraspanins promote MHC multimerisation are discussed.
authors.affiliation: The Burnet Institute of Medical Research and Public Health, A&RMC, Heidelberg, Australia.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Sheng
authors.forename: Annemiek B
authors.initials: AB
authors.lastname: van Spriel
authors.forename: Kate H
authors.initials: KH
authors.lastname: Gartlan
authors.forename: Mariam
authors.initials: M
authors.lastname: Sofi
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
authors.forename: Leonie
authors.initials: L
authors.lastname: Ashman
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wright
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060185:Tetraspanin 24; D059470:Tetraspanins
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C554716:Cd151 protein, mouse; C504565:Cd37 protein, mouse; D006023:Glycoproteins; D060185:Tetraspanin 24; D059470:Tetraspanins