T cell responses are governed by avidity and co-stimulatory thresholds.
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.
Bachmann
M F
MF
Ontario Cancer Institute Department of Medical Biophysics, Toronto, Canada.
Sebzda
E
E
Kündig
T M
TM
Shahinian
A
A
Speiser
D E
DE
Mak
T W
TW
Ohashi
P S
PS
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*
D018106:CD28 Antigens; D016207:Cytokines; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell