title: CD43 is a murine T cell costimulatory receptor that functions independently of CD28.
abstract: Costimulation mediated by the CD28 receptor has been shown to play an important role in the development of a vigorous T cell immune response. Nevertheless, CD28-deficient mice can mount effective T cell-dependent immune responses. These data suggest that other costimulatory molecules may play a role in T cell activation. In a search for other costimulatory receptors on T cells, we have characterized a monoclonal antibody (mAb) that can costimulate T cells in the absence of accessory cells. Similar to CD28 antibodies, this mAb, R2/60, was found to synergize with T cell receptor engagement in inducing proliferation. Independent ligation of CD3 and the ligand recognized by R2/60 results in T cell proliferation, suggesting that the two molecules do not have to colocalize to activate the R2/60 costimulatory pathway. R2/60 does not react with CD28, and furthermore, R2/60 costimulates in a CD28-independent fashion since the mAb costimulates T cells from the CD28-deficient mice as well as wild-type mice. Expression cloning of the R2/60 antigen identified the ligand as murine CD43. Together, these data demonstrate that CD43 can serve as a receptor on T cells that can provide CD28-independent costimulation.
authors.affiliation: Ben May Institute, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Sperling
authors.forename: J M
authors.initials: JM
authors.lastname: Green
authors.forename: R L
authors.initials: RL
authors.lastname: Mosley
authors.forename: P L
authors.initials: PL
authors.lastname: Smith
authors.forename: R J
authors.initials: RJ
authors.lastname: DiPaolo
authors.forename: J R
authors.initials: JR
authors.lastname: Klein
authors.forename: J A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D015703:Antigens, CD; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology*; D017252:CD3 Complex / Q000276:immunology; D051917:Leukosialin; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012795:Sialoglycoproteins / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D051917:Leukosialin; D008024:Ligands; D012795:Sialoglycoproteins; C497863:Spn protein, mouse