Experimental confirmation of the C3 tickover hypothesis by studies with an Ab (S77) that inhibits tickover in whole serum

The complement component 3 (C3) tickover hypothesis was put forward in the early 1970s to account for the spontaneous activation of the alternative complement pathway that occurs after the genetic absence or in vitro depletion of Factor I, the enzyme that is essential for the breakdown of C3b. The hypothesis was widely accepted, but experimental demonstration of the tickover was elusive. A phage Ab against C3b that inhibited the alternative complement pathway, but not the classical pathway, was described in 2009. Studies using this Ab in a variety of assays have now demonstrated that it acts primarily by inhibiting tickover, thereby confirming that tickover really exists.