Biological Roles of Lectins in Innate Immunity: Molecular and Structural Basis for Diversity in Self/Non-Self Recognition

摘要

Lectins and other pattern recognition proteins are critical components of innate immune mechanisms in invertebrates and vertebrates. Unlike immunoglobulins, TCRs, and VLRs, which generate diversity in recognition by genetic recombination, lectins like most innate immune receptors are "hard-wired" in the germline. Therefore, one of the outstanding questions is how the innate immune system is able to cope with the great diversity of potential microbial infectious challenges. Although the concept of pattern recognition proposes that only a handful of microbial conserved surface molecules need to be recognized for successful innate immune defense, the highly diversified microbial communities to which all organisms are exposed to and the dynamic changes in surface expression components suggests that a substantial diversity in non-self recognition mechanisms may be required for immune protection. The detailed analysis of the structural basis of leetin ligand binding and the diversity and complexity of the leetin repertoires in taxa that lack adaptive immunity, such as invertebrates, strongly suggests that this is the case. Further, recent studies have extended these observations to ectothermic vertebrates. In this review we focus on C-type and F-type lectins to illustrate how in the absence of genetic rearrangement, a substantial degree of diversity in recognition and effector functions is still achieved. The presence of multigene families, tandemly arrayed polymorphic recognition domains, formation of chimeric structures by exon shuffling, and a considerable "plasticity" of their carbohydrate binding sites further contribute to expand the ligand recognition spectrum and functional diversification of lectins as innate immune receptors.