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

The ability of the immune system to respond by ridding a pathogen without debilitating the host depends upon the ability of the effector T(h) (eT(h)) 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 T(h) (iT(h)) 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 eT(h) anti-non-self and an insufficiency of eT(h) anti-self based on two postulates. (i) An antigen-independent pathway to a priming level of eT(h) anti-non-self under conditions where iT(h) 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 iT(h) and 'primer' eT(h) 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.