A novel postpriming regulatory check point of effector/memory T cells dictated through antigen density threshold-dependent anergy

摘要: CTLs act as the effector arm of cell-mediated immune system to kill undesirable cells. Two processes regulate these cells prevent self reactivity: a thymic selection process that eliminates autoreactive clones and multistage activation or priming endows them with license cognate target Hitherto no subsequent regulatory restrictions have been ascribed for properly primed activated are licensed kill. In this study we show possess novel postpriming mechanism(s) influences outcome their encounter This mechanism gauges degree Ag density, whereupon reaching certain threshold significant changes occur induce anergy in T The biological consequences Ag-induced control includes alterations expression cell surface molecules immunological synapse activity cytokine profiles retarded proliferation. Most profound is genome-wide microarray analysis demonstrates genes related membrane potential, TCR signal transduction, energy metabolism, cycle control. Thus, discernible unique gene signature response high density has observed. Consequently, properties self-referential sensory organ. These studies identify new CTL anergenic-like properties. extends our understanding function regulation such peripheral tolerance, viral infections, antitumor responses, hypersensitivity, autoimmunity.