The historical postulate: Is it the basis, at the level of the system, for self?nonself discrimination?

Burnet envisaged the early presence of self-antigens in development, or ‘the history’ an animal, ablates animal's ability to immunologically respond against them. Lederberg added idea that continuous is required maintain tolerance throughout life. We refer Lederberg's proposal as ‘The Historical Postulate’. The mechanism central tolerance, now understood, consistent with Postulate. Some observations, reflecting peripheral appear inconsistent this postulate. For example, some foreign tissues, grafted onto animal before immune system develops, can be rejected matures. original two-signal model lymphocyte activation was proposed part because it accounted for a manner antigen-mediated cooperation, whereas antigen would inactivate lymphocytes when insufficient number achieve activation. argue here exceptions Postulate explained by activation: they reflect existence greater numbers specific these antigens than natural antigens, and so are outside physiological limits important selecting through evolution tolerance. consideration whether valid important, even if only within certain understandable limits. currently popular DAMP CD4 T cell is, strictly speaking we discuss, violation