Review examines mechanisms of self/nonself-recognition and origins of vertebrate adaptive immunity.
The ability to discriminate self from nonself is found throughout the tree of life and underlies a diverse range of processes, including immunity, mate choice, and cooperative social interactions. Self-/nonself-recognition also operates during development, for example, coordinating the formation of complex neural circuits. Despite this ubiquity, proteins that mediate self-/nonself-recognition are lineage-specific. Novel genetic interactions have arisen repeatedly and in a punctuated manner, in some cases even evolving de novo within the same lineages. This review examines the fundamental principles of self-/nonself-recognition across diverse taxa, focusing on the cellular and molecular mechanisms underlying discrimination, the generation and maintenance of novel recognition specificities, and how these systems have been modified over time. Together, these modifications provide a mechanistic foundation to address a central problem in evolutionary biology: the origins of vertebrate adaptive immunity, a system capable of unparalleled self-/nonself-discrimination.
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Tomaso et al. (2026) studied this question.
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