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A stepwise model of polyreactivity of the T cell antigen-receptor (TCR): its impact on the self–nonself discrimination and on related observations (receptor editing, anergy, dual receptor cells)

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Abstract

The existence of antigen-receptors, BCR, and T cell antigen-receptors, that are “polyreactive”, necessitates a rethinking of its effect on two problems faced by the “adaptive” immune system: the self (S)–nonself (NS) discrimination and the determination of effector class. Here, we will concentrate on the impact of polyreactivity on the S–NS discrimination. The anti-S cells interacting with S (i.e., responding to Signal 1) are on the pathway to inactivation. Before irreversibility sets in, these cells can be activated by a second signal (Signal 2) from an effector T-helper (eTh). As these polyreactive anti-S cells express anti-NS specificities, they can be activated by recognition of NS-epitopes in the host’s normal immunogenic load with the potential to result in autoimmunity. This problem is delineated using a discrete structural model, the corollaries of which are: (1) a two-step pathway for the purging of anti-S cells (i.e., the S–NS discrimination), and (2) defensible contexts within which to view the phenomena of receptor editing, anergy, and dual receptor cells.

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

    Melvin Cohn

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  1. Melvin Cohn
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Correspondence to Melvin Cohn.

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Cohn, M. A stepwise model of polyreactivity of the T cell antigen-receptor (TCR): its impact on the self–nonself discrimination and on related observations (receptor editing, anergy, dual receptor cells). Cell. Mol. Life Sci. 71, 2033–2045 (2014). https://doi.org/10.1007/s00018-013-1540-9

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  • DOI: https://doi.org/10.1007/s00018-013-1540-9

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