The Role of Idiotype in T-Cell Regulatory Events (original) (raw)

The Biology of Idiotypes, 1984

Abstract

In his original proposal of an immunoregulatory network of lymphocytes, Jerne proposed that the naive immune system is in a negatively regulated state.(1) Before the introduction of antigen, a lymphocyte specific for a certain antigenic determinant (epitope) is held in check by another lymphocyte’s anti-idiotypic receptor. In this network all antibodies represent anti-idiotypes. The appearance of antigen perturbs this homeostatic down-regulation and an immune response is generated. As a consequence of the immune response to the individual epitopes, the amount of antigen is reduced below a threshold level whereupon the systems returns to homeostasis. In recent years, the mechanism by which the immune response is regulated has been investigated. Antigen-specific(2) and nonspecific(3) T-suppressor (Ts) cells play a critical role in this regulation. Further, idiotype-anti-idiotype interactions may be important in both Ts—target cell and Ts—Ts interactions. However, rather than existing in a down-regulated state before the appearance of an antigen, the immune system can be thought of as a complex set of dynamically activated and regulated cellular elements. Antigen stimulates an immune response (postive) and then initiates immunoregulatory (negative) events, instead of simply perturbing homeostatic regulation. Differential antigen presentation to T-helper (Th) and Ts cells by specific antigen-presenting cells (APCs) may shift this delicate balance from immunity to immune regulation. It appears that presentation of antigen by an I-A+ I-J− APC activates Th(4) cells, while an I-J+ I-A− APC activates Ts cells.(5) Moreover, differential expression of I-A- or I-J- encoded molecules on APCs might mediate these processes. On the other hand, T-cell idiotypes may serve as cell interaction molecules in immunoregulatory events subsequent to Ts activation.(6)

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