Abstract
Abstract Adaptive immunity emerged in jawed vertebrates exhibiting the ability to express somatically rearranged antigen receptor genes with combinatorial binding sites consisting of residues from each of the paired v-type (variable) Ig domains (i.e., VαVβ). The origins of contemporary antigen receptors have been described by a model in which an ancestral Ig gene diversified to form polymorphic variants consisting of an antigen binding domain linked to an effector module (i.e., VC). The high degree of clustering of polymorphic residues at the combining site between v-type Ig domains throughout evolution of adaptive immunity suggests that this feature confers a powerful advantage in creating a diverse repertoire of antigen receptors. To address the origins of adaptive immunity, we solved the crystal structure of VCBP3 D1 and D2 from the cephalochordate Branchiostoma floridae, which has characteristics of a primordial antigen receptor: a high degree of germline encoded polymorphism and paired v-type Ig domains with polymorphism clustered at the combining site. In addition to finding combinatorial recognition in a jawless invertebrate, we solved the structure of a primordial V domain to 1.15 Å, a level of refinement that permits new insight into the atomic basis for Ig domain organization and stability.
Published Version
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