Functional Analysis of Two Divergent C4 Isotypes in the Classical and Lectin Pathways of Complement Activation in the Common Carp (Cyprinus carpio)

In the evolution of complement system, a major humoral innate immune factor, existence multiple isotypes components is considered as key strategy to enhance defense. Complement C4 also diversified in wide range vertebrate species including teleost fish, possibly supporting robust activation mechanism complement. To better understand functional diversity two isotypes, C4-1 and C4-2, sharing only 32% amino acid sequence identity, were examined for binding specificities towards model target molecules representing microbe antigens Gram-positive -negative bacteria. The results suggest that C4-2 behave similarly tested targets, despite predicted difference specificity based on thioester catalytic site. participation classical lectin pathways was explored using pathway-specific activating enzyme complexes, C1r/s MBL-MASP2. As result, can be activated both pathways, at higher efficiency pathway. Taken together, present imply are fully cascades, probably playing comparable roles immunity.