Two types of antigen receptor systems in vertebrates.

Extant jawless vertebrates, represented by lampreys and hagfishes, have innate immune receptors with variable domains structurally resembling those of T/B-cell receptors. However, they appear to lack cardinal elements of adaptive immunity shared by all jawed vertebrates: major histocompatibility complex molecules and T/B-cell receptors. Thus, it was widely believed that adaptive immunity is unique to jawed vertebrates. Recently, this belief was overturned by the discovery of agnathan antigen receptors named 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 and bind antigens with high specificity and avidity. The fact that variable lymphocyte receptors are structurally unrelated to T/B-cell receptors indicates that jawed and jawless vertebrates have developed antigen receptors independently.