A computerized model for the self—non-self discrimination at the level of the Th (Th genesis). I. The origin of ‘primer’ effector Th cells

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Abstract
The ability of the immune system to respond by ridding a pathogen without debilitating the host depends upon the ability of the effector Th (eTh) to make a discrimination between ‘self’ and ‘non‐self’ antigens. This ability is somatically learned and involves the sorting of the somatically generated random repertoire of initial state Th (iTh) into two classes of specificity: one, anti‐self, the functional expression of which must be inactivated; the other, anti‐non‐self, the functional expression of which must be activated. We propose a model for the origin of a sufficiency of eTh anti‐non‐self and an insufficiency of eTh anti‐self based on two postulates. (i) An antigen‐independent pathway to a priming level of eTh anti‐non‐self under conditions where iTh anti‐self are effectively deleted by interaction with self. This state is established during a window of fetal development and maintained throughout life because self is persistent. (ii) Associative recognition of antigen (peptide–MHC class II) on an antigen‐presenting cell between iTh and ‘primer’ eTh that results in the rapid induction of an effective level of helper activity to non‐self antigen. A computer simulation is provided that enables evaluation of this model.