Progress of adaptive immunity system of agnathan vertebrates

Extant jawless vertebrates, represented by lampreys and hagfishes, have innate immune receptors with variable domains structurally resembling T/B-cell receptors. However, they lack cardinal elements of adaptive immunity shared by all jawed vertebrates: T/B-cell receptors and major histocompatibility complex molecules. Thus, it is widely believed that adaptive immunity is unique to jawed vertebrates. Recently, this belief was overturned by the discovery of agnathan antigen receptors, known as variable lymphocyte receptors. These receptors generate diversity in their antigen-binding sites through assembling highly diverse leucine-rich repeat modules. The crystal structures of hagfish variable lymphocyte receptor monomers indicate that they adopt a horseshoe-shaped structure and likely bind antigens through the hypervariable concave surface. Secreted variable lymphocyte receptors form pentamers or tetramers of dimers bind antigens with high specificity and avidity. This indicates that jawed and jawless vertebrates have developed antigen receptors independently. This paper provides valuable clues for studying the origin and evolution of adaptive immunity system.