Neutralization of activity as indicated by a recovery of hemolysis, was observed only on IxAC-B1. or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences experienced undergone diversifying ROR agonist-1 selection. Diversification was not associated with structural, biochemical or functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusions/Significance Anticomplement proteins from are the first inhibitors that specifically target a positive regulator of match, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative match pathway. Looking for and detecting the different selection pressures involved will help in understanding the development of multigene families and hematophagy in arthropods. Introduction Parasites probably impact every living organism and it may reasonably be estimated that at least half the animals on earth are parasites [1]. By definition, parasites live at the expense of their host but hosts defend themselves and, in turn, parasites evolve counter-measures. Parasitism is probably therefore a major driving pressure in development [1]. Bloodfeeding arthropods such as ticks constitute a very good example of the evolutionary arms race between hosts and parasites. Ticks are obligate blood feeding arachnids. They infest many species of mammals, birds, reptiles and amphibians worldwide. They are the vectors of protozoan, bacterial and viral pathogens of primary medical and veterinary importance. Examples of such important pathogens are or or hard ticks and or soft ticks. The family is usually further divided into two subdivisions: Prostriata, which contains only the subfamily and female is typically 7C10 days [3]. Such a long blood meal is only possible because these parasites have developed ways to circumvent host defense mechanisms including hemostasis (coagulation, platelet aggregation and vasoconstriction), the inflammatory response and innate and adaptive immunity [examined in 5], [6], [7], [8]. Furthermore, pain or itching caused by the inflammatory response stimulates ROR agonist-1 hosts to scrape and dislodge the parasite. The complement system is a first line of defence against invading pathogens and it links the innate and adaptive responses of the vertebrate immune system [examined in 9]. It consists of a cascade of plasma enzymes leading to activation of three effector mechanisms: (i) generation of the short potent pro-inflammatory peptides C3a and C5a, ii) deposition of opsonizing C3b proteins on cell BTF2 surfaces, (iii) formation of the membrane attack complex (MAC). MACs produce pores in the membrane, leading to cell death. Match is activated three main pathways. The classical pathway (CP) is initiated mainly when the C1 complex binds to the Fc region of certain antibody isotypes in immune complexes. The lectin-mediated pathway is usually activated by mannose-binding lectin interacting ROR agonist-1 with mannose residues on microbial surfaces. The alternative pathway (AP) is usually spontaneously activated by ROR agonist-1 hydrolysis of plasma C3 into C3 (H2O). C3 (H2O) binds soluble factor B (fB). Bound fB is usually cleaved by serine protease factor D into soluble Ba peptide and the larger Bb fragment. The producing C3 (H2O)Bb complex is the initial C3 convertase. It cleaves fluid-phase C3 into C3a peptide and metastable C3b. C3b binds covalently to a pathogen or cell surface via a short-lived thioester bond. Factor B interacts with C3b, leading to its cleavage by factor D and the formation of the C3 convertase ROR agonist-1 (C3bBb). This complex generates new C3b molecules and amplifies the match cascade by forming new C3 convertases or C5 convertases (C3b2Bb). C5 convertase cleaves C5 into C5a and C5b. C5b initiates the formation of MAC [9]..