Download Annual Review of Immunology Volume 12 1994 by Annual Reviews PDF

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As I have said, Lederberg (37), by example, illustrated the three questions to be answered if we were to develop a theory of the S/NS discrimination. Weknew that the theory of Lederberg no longer fit the data (47, 48); it was someyears before I realized that the theory was wrong on a priori grounds, because mutation to anti-self in an inducible-only cell would be lethal and such mutations are unavoidable (32). Forsdyke (46) gave us the barest of hints as to what a competing theory would entail.

While the emotional hindsights characterizing the biographies written by nonhistorians are delightful reading, muchmore is learned by the criticisms of a thoughtful colleague than by the adoration of the Magi. This commentin no way need detract from the inspirational leadership of great people. Accordingto Sexton (44), Burnet felt he deserved two Nobel prizes: one for his insight on the origin of tolerance, for whichhe did receive the prize, the other for clonal selection theory, for whichhe did not receive the prize.

Important for this exchange was the first attempt on our part to tie together two decision functions, the S/NS discrimination and the determination of the class of this response (59, 60). In 1978, as I described elsewhere (3, foreword), the formalization of the concept of restrictive recognition of antigen by Langman(61) led us (62) to redefine the mechanism of the eTH-iT/iB interaction as due to two unispecific cells in which the effector T helper (eTH) initiated and sent Signal [2] via the class II-restricting element on the target iT/iB-cell.

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