A two-step, two-signal model for the primary activation of precursor helper T cells

Abstract

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.

Figure 1

Contemporary models for the activation of pTh cells. For a detailed explanation, see the text. The generation of signal 1 alone results in inactivation, whereas activation requires the generation of both signal 1 and signal 2 (costimulatory signal).

Figure 2

The original two-signal model. The generation of signal 1 alone results in inactivation, whereas activation requires the generation of both signal 1 and signal 2.

Figure 3

A two step, two-signal model for the primary activation of pTh cells. For an explanation, see the text.