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International Immunology, Vol. 14, No. 10, pp. 1105-1112, October 2002
© 2002 Japanese Society for Immunology

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

Melvin Cohn1, Rodney E. Langman{dagger},1 and James J. Mata1

1 Conceptual Immunology Group, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

{dagger}It is with great sadness that we report the death of Dr Rodney E. Langman on 13 August 2002.Correspondence to: M. Cohn; E-mail: cohn{at}salk.edu
Transmitting editor: S. M. Hedrick,

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.

Keywords: computer simulation, origin of effector Th, self–non-self discrimination, tolerance, two-signal model


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