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)

• Published in: Cellular and molecular life sciences : CMLS Vol. 71; no. 11; pp. 2033 - 2045
• Main Author: Cohn, Melvin
• Format: Journal Article
• Language: English
• Published: Basel Springer-Verlag 01.06.2014; Springer Basel; Springer Nature B.V
• Subjects: Adaptive Immunity; Animals; Antigens; Autoimmunity; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; cells; Clonal Anergy; discrimination; effectors; Epitopes - genetics; Epitopes - immunology; Gene Expression Regulation - immunology; Humans; Immune system; Life Sciences; Models, Immunological; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Review; Self Tolerance; Signal transduction; T cell receptors; T-Cell Antigen Receptor Specificity; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-lymphocytes; Autoimmunity; TCR; Anergy; Polyreactivity; Self–nonself discrimination; Receptor editing; Dual receptor cells
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-013-1540-9

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.