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Semin Immunol. 2000 Jun;12(3):189-95; discussion 257-344.

A minimal model for the self-nonself discrimination: a return to the basics.

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Conceptual Immunology Group, The Salk Institute for Biological Studies, La Jolla, CA 92117, USA.


An immune system is required in any host that evolves slowly relative to the pathogens that attack it. This immune system must somatically generate and regulate new specificities. We propose a mechanism that results in a self-nonself discrimination that is a one-time regulatory event, which occurs early in development when maternal protection ensures an environment that is free of nonself. Our proposed mechanism considers all T and B cells to arise in an i-state which is incapable of effector reactions. Uniquely in iTh (helpers) a prolonged absence of antigen permits their differentiation to eTh (only nonself antigens are absent). In all i-state cells antigen induces an anticipatory a-state which, in the presence of eTh and via associative recognition of antigen results in the e-state, and which in the absence of eTh results in cell death.

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