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Activation rules: the two-signal theories of immune activation

Nature Reviews Immunology volume 2, pages 439–446 (2002)Cite this article

Abstract

Two-signal theories of lymphocyte activation have evolved considerably over the past 35 years. In this article, we examine the contemporary experimental observations and theoretical concerns that have helped to forge the most influential variants of the theory. We also propose that more-rigorous quantitative methods are required to sustain theoretical development in the future.

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Figure 1: The evolution of Bretscher and Cohn's associative recognition model.
Figure 2: Kevin J. Lafferty.
Figure 3: The development of the two-signal theory in Kevin Lafferty's laboratory.

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Acknowledgements

We are grateful to the following people for their recollections, suggestions, input and advice: A. Basten, J. F. A. P. Miller, K. Lafferty (deceased), C. Simeonovic, B. Fazekas and C. Jolly. A.G.B. is the recipient of an interim fellowship from the Australian National Health and Medical Research Council (NHMRC). P.D.H. is the recipient of a senior fellowship from the NHMRC. We dedicate this article to the memory of Kevin Lafferty. His remarkable contributions to the study of T-cell activation and alloreactivity will be long remembered, and his forceful advocacy for reason in scientific endeavour will be sadly missed.

Author information

Authors and Affiliations

  1. the Centenary Institute of Cancer Medicine and Cell Biology, Locked bag #6, Newtown, 2042, New South Wales, Australia

    Alan G. Baxter

  2. the Walter and Eliza Hall Institute, c/o Post Office, Royal Melbourne Hospital, Parkville, 3050, Victoria, Australia

    Philip D. Hodgkin

Authors
  1. Alan G. Baxter
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  2. Philip D. Hodgkin
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Correspondence to Alan G. Baxter.

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DATABASES

Entrez

Bordetella pertussis

Mycobacterium tuberculosis

LocusLink

CD3

CD40

CD40L

CD80

CD86

IL-1

IL-2

IL-4

IL-6

IL-8

NF-κB

Toll

Toll-like receptors

FURTHER INFORMATION

Bright Sparcs Biography — Frank Macfarlane Burnet

NOBEL e-MUSEUM — Karl Landsteiner

NOBEL e-MUSEUM — Peter C. Doherty and Rolf M. Zinkernagel (Nobel Prize in Physiology or Medicine 1996)

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Baxter, A., Hodgkin, P. Activation rules: the two-signal theories of immune activation. Nat Rev Immunol 2, 439–446 (2002). https://doi.org/10.1038/nri823

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