Two signal models for lymphocyte activation build on the Talmage/Burnet concept that receptor diversity is generated within the immune system by a random process, and that individual lymphocytes carry a single receptor on their surface that determines their specificity. Such models cannot use a concept of signal one anergy (or deletion) to explain the maintenance of self-tolerance in terms of the Bretscher/Cohn theory if they abandon the concept of associative recognition.
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Lafferty et al. (1993) studied this question.
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