A Two-Step, Two-Signal Model for the Primary Activation of Precursor Helper T Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 1; pp. 185 - 190
• Main Author: Bretscher, Peter A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 05-01-1999; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Antigen Presentation; Antigens; Autoantigens; B lymphocytes; Biological Sciences; Epitopes; Histocompatibility Antigens Class II; Immune system; Immune Tolerance; Immunology; Lymphocyte Activation; Lymphocytes; Models, Immunological; Molecules; Receptors; Signal Transduction; T lymphocytes; T lymphoid precursor cells; T-Lymphocytes, Helper-Inducer - immunology; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.1.185

I present here a new model for the primary activation of precursor helper T cells. Observations demonstrate that the immune system learns not to respond to extrathymic, organ-specific self-antigens because of their early appearance in development. The immune system thus discriminates between peripheral self-antigens and foreign antigens and, when mature, usually makes an immune response against only the latter. Contemporary models for the activation and inactivation of T helper (Th) function do not account for such discrimination. The model proposed here is consistent with contemporary findings and incorporates a mechanism of peripheral self-nonself discrimination.