title: CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics.
abstract: The structurally related T cell surface molecules CD28 and CTLA-4 interact with cell surface ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APC) and modulate T cell antigen recognition. Preliminary reports have suggested that CD80 binds CTLA-4 and CD28 with affinities (Kd values approximately 12 and approximately 200 nM, respectively) that are high when compared with other molecular interactions that contribute to T cell-APC recognition. In the present study, we use surface plasmon resonance to measure the affinity and kinetics of CD80 binding to CD28 and CTLA-4. At 37 degrees C, soluble recombinant CD80 bound to CTLA-4 and CD28 with Kd values of 0.42 and 4 microM, respectively. Kinetic analysis indicated that these low affinities were the result of very fast dissociation rate constants (k(off)); sCD80 dissociated from CD28 and CTLA-4 with k(off) values of > or = 1.6 and > or = 0.43 s-1, respectively. Such rapid binding kinetics have also been reported for the T cell adhesion molecule CD2 and may be necessary to accommodate-dynamic T cell-APC contacts and to facilitate scanning of APC for antigen.
authors.affiliation: Medical Research Council Cellular Immunology Unit, Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
authors.forename: P A
authors.initials: PA
authors.lastname: van der Merwe
authors.forename: D L
authors.initials: DL
authors.lastname: Bodian
authors.forename: S
authors.initials: S
authors.lastname: Daenke
authors.forename: P
authors.initials: P
authors.lastname: Linsley
authors.forename: S J
authors.initials: SJ
authors.lastname: Davis
mesh_terms: D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D001483:Base Sequence; D018106:CD28 Antigens / Q000378:metabolism*; D060908:CTLA-4 Antigen; D006801:Humans; D018796:Immunoconjugates; D007700:Kinetics; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D011948:Receptors, Antigen, T-Cell; D000069594:Abatacept