Annual Review of Immunology Volume 12 1994 by Annual Reviews

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Second, Signal [2] is obligatory for induction under this model; the "helper" concept was that the signalling role, if it existed, would be facultative (frequently normally bypassed). Three beautiful papers analyzing this stage in our thinking were written by Bretscher (50, 55, 56). By 1973, it was clear to us that we were dealing with an effector T- Annual Reviews Annu. Rev. Immunol. 12:1-62. org by HINARI on 08/30/07. For personal use only. ON THINKING AND WISDOM 37 helper(eTr~)--iT/iB interaction that did not involve secreted antibody for which I had used the symbol IgT in 1971 (54).

This is linked or associative recognition of antigen. Thus, Signals [1] and [2] were separated but delivered simultaneously or in close sequence to the same i-cell. In 1971, we (50, 54) made the "carrier antibody" cytophilic for effector cell (a carrier specific cell). This latter delivered Signal [2] associative recognition of antigen boundto the i-cell. It seemedunrealistic at the time to propose a cell-cell antigen-driven interaction between two unispecific cells because, for an effective response, they were expected to take too long a time to find each other.

It is safe to say that we never learned anything from it. Although from mypoint of view, the idiotype network theory of regulation lacked logic and rationale, for the sake of history, it is worth this comment. The theory is one more byproduct of the Landsteiner legacy. During the instructionist era the assumption that antigen acted as a template led automatically to a network theory in which antigen molded antibody and the new antibody, acting as a template (experimentally provided in the form of antigen-antibody complexes), induced anti-antibody.

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