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Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes

Nature Immunology volume 6, pages 65–72 (2005)Cite this article

An Erratum to this article was published on 01 February 2005

Abstract

Signaling through the T cell antigen receptor leading to elimination (negative selection) or differentiation (positive selection) of developing thymocytes generates a self-tolerant T cell repertoire. Here we report that the serine-threonine kinase MINK selectively connects the T cell receptor to a signaling pathway that mediates negative but not positive selection. Analysis of this pathway suggested that the essential function of MINK in the elimination of self-reactive thymocytes may be associated with 'downstream' activation of Jun kinase and enhancement of expression of the proapoptotic molecule Bim.

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Figure 1: MINK expression in bone marrow and thymocyte subpopulations.
Figure 2: Characterization of MINK-deficient mice.
Figure 3: MINK expression is required for deletion of Vβ5+ TCR cells by the Mtv-9 endogenous superantigen.
Figure 4: Peptide-induced deletion of autoreactive thymocytes in mice expressing an MHC class II– or class I–restricted TCR transgene.
Figure 5: Analysis of upstream events in the MINK-dependent signaling pathway.
Figure 6: Analysis of downstream events in the MINK-dependent signaling pathway.

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Acknowledgements

We thank J. Levecchio for cell sorting; K. Akashi for discussions and critical comments; and A. Angel for assistance with the manuscript and figures. Supported by National Research Service Award (T32 AI07386 to N.M.).

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Authors and Affiliations

  1. Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute and Department of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Nami McCarty, Silke Paust, Koichi Ikizawa, Xiaoyan Li & Harvey Cantor

  2. Division of Food Engineering, National Food Research Institute 2-1-12, Kannondai, Tsukuba, 305, Ibanaki, Japan

    Ippeita Dan

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  1. Nami McCarty
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Correspondence to Harvey Cantor.

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Supplementary information

Supplementary Fig. 1

Sorting of thymic subpopulations for real time PCRs. (PDF 201 kb)

Supplementary Fig. 2

Additional analysis of MINK mice. (PDF 273 kb)

Supplementary Fig. 3

Additional analysis of HY MINK and HY control chimeric mice. (PDF 149 kb)

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McCarty, N., Paust, S., Ikizawa, K. et al. Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. Nat Immunol 6, 65–72 (2005). https://doi.org/10.1038/ni1145

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