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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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.
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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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DOI: https://doi.org/10.1038/nri823
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