Self-referential immune recognition through C-type lectin receptors.

The term "lectin" is derived from the Latin word lego- (aggregate) (Boyd & Shapleigh, 1954). Indeed, lectins' folds can flexibly alter their pocket structures just like Lego blocks, which enables them to grab a wide-variety of substances. Thus, this useful fold is well-conserved among various organisms. Through evolution, prototypic soluble lectins acquired transmembrane regions and signaling motifs to become C-type lectin receptors (CLRs). While CLRs seem to possess certain intrinsic affinity to self, some CLRs adapted to efficiently recognize glycoconjugates present in pathogens as pathogen-associated molecular patterns (PAMPs) and altered self. CLRs further extended their diversity to recognize non-glycosylated targets including pathogens and self-derived molecules. Thus, CLRs seem to have developed to monitor the internal/external stresses to maintain homeostasis by sensing various "unfamiliar" targets. In this review, we will summarize recent advances in our understanding of CLRs, their ligands and functions and discuss future perspectives.