The Journal of Experimental Medicine
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Published online October 15, 2007
doi:10.1084/jem.20070254
The Journal of Experimental Medicine, Vol. 204, No. 11, 2553-2559
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Naeher et al.
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BRIEF DEFINITIVE REPORT

 A constant affinity threshold for T cell tolerance

Dieter Naeher1, Mark A. Daniels1, Barbara Hausmann1, Philippe Guillaume2, Immanuel Luescher2, and Ed Palmer1

1 Laboratory of Transplantation Immunology, Department of Research, University Hospital, 4031 Basel, Switzerland
2 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland

CORRESPONDENCE Ed Palmer: ed.palmer{at}unibas.ch

T cell tolerance depends on the T cell receptor's affinity for peptide/major histocompatibility complex (MHC) ligand; this critical parameter determines whether a thymocyte will be included (positive selection) or excluded (negative selection) from the T cell repertoire. A quantitative analysis of ligand binding was performed using an experimental system permitting receptor–coreceptor interactions on live cells under physiological conditions. Using three transgenic mouse strains expressing distinct class I MHC–restricted T cell receptors, we determined the affinity that defines the threshold for negative selection. The affinity threshold for self-tolerance appears to be a constant for cytotoxic T lymphocytes.

Abbreviations used: ABA, azidobenzoic acid; DP, double-positive; FTOC, fetal thymus organ culture; PbCS, Plasmodium berghei circumsporozoite; pMHC, peptide/MHC; SP, single-positive.


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