title: 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).
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.
authors: Conceptual Immunology Group, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA, 92037, USA, cohn@salk.edu.
authors: Melvin
authors: M
authors: Cohn
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015551:Autoimmunity; D017635:Clonal Anergy; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D017634:Self Tolerance; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
chemical_list: D000939:Epitopes; D011948:Receptors, Antigen, T-Cell