title: T cell responses are governed by avidity and co-stimulatory thresholds.
abstract: We analyzed the avidity and CD28-mediated co-stimulatory requirements for the activation of T cells in vivo and in vitro. The strength of the T cell/antigen-presenting cell interaction was varied by using altered peptide ligands for stimulation. Co-stimulatory requirements were studied using T cells from CD28-deficient mice. The results indicate that T cell activation is not an all-or-nothing event, but occurs in distinct steps. For each step, a certain avidity, co-stimulatory threshold or both, must be met. Depending upon the strength of the interaction between the T cell receptor and the major histocompatibility complex/peptide and the presence of CD28 co-stimulatory signals, T cells may undergo blast formation alone or proliferate or eventually both proliferate and differentiate to effector cells. Thus, T cell activation is governed by both avidity and co-stimulatory thresholds.
authors.affiliation: Ontario Cancer Institute Department of Medical Biophysics, Toronto, Canada.
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: E
authors.initials: E
authors.lastname: Sebzda
authors.forename: T M
authors.initials: TM
authors.lastname: Kündig
authors.forename: A
authors.initials: A
authors.lastname: Shahinian
authors.forename: D E
authors.initials: DE
authors.lastname: Speiser
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.forename: P S
authors.initials: PS
authors.lastname: Ohashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018106:CD28 Antigens / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D006649:Histocompatibility Antigens / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018106:CD28 Antigens; D016207:Cytokines; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell