Alternative Self or Nonself Recognition of an Antigen Expressed in a Rare Cell Type in Transgenic Mice: Implications for Self-tolerance and Autoimmunity

During its development, the immune system acquires the ability to recognize and respond to a wide variety of cells and other entities from the outside environment (Hood et al. 1984; Roitt et al. 1985). A necessary feature of this capacity is the ability to discriminate between what is a normal component of the body (self) and what is not (foreign or nonself). The existence of immunological tolerance toward self has been well-established for many years, and mechanisms that could serve to achieve it have been postulated and increasingly refined as our knowledge of the development, organization, and function of the immune system has progressed (Burnet 1959; Dresser and Mitchison 1968; Bretscher and Cohn 1970; Weigle 1973; Howard and Mitchison 1975; Nossal 1983; Schwartz 1989). The importance of self-tolerance can be seen in the damages wrought by autoimmune diseases, such as insulin-dependent diabetes, in which the immune system becomes self-reactive against...