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International Immunology Advance Access originally published online on August 14, 2009
International Immunology 2009 21(10):1151-1161; doi:10.1093/intimm/dxp081
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses

Michiyo Imada1, Kyoko Masuda2, Rumi Satoh2, Yumi Ito1, Yoshiyuki Goto1, Takayuki Matsuoka1, Shota Endo1, Akira Nakamura1, Hiroshi Kawamoto2 and Toshiyuki Takai1

1 Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo 4-1, Sendai 980-8575, Japan
2 Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, 1-7-22, Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan

Correspondence to: T. Takai; E-mail: tostakai{at}idac.tohoku.ac.jp

Activated mature T cells induce various inhibitory receptors implicated in maintaining peripheral tolerance in response to the trans-acting ligands. Interestingly, paired Ig-like receptor (PIR)-B, an inhibitory MHC class I receptor on B cells and myeloid cells, could be involved in regulating early T cell development because epitope for PIR is detected on pre-thymic T/NK progenitors but not on thymocytes or mature T cells. We hypothesized that PIR-B is not only a regulator for T cell development but is also detrimental if expressed on mature T cells. Here we demonstrated, using PIR-B-deficient fetuses, that PIR-B is indeed expressed on the T cell progenitors but failed to identify its distinctive roles in the development. Forced expression of PIR-B in thymocytes and mature T cells also resulted in no abnormalities in development. However, upon antigenic or allogeneic stimulation, peripheral T cells with the ectopic PIR-B showed reduced Th type 1 responses due to the suppression of proximal TCR signaling by constitutive binding of PIR-B to MHC class I on the same cell surface. Our findings suggest that T cell expression of PIR-B with the cis-interacting MHC class I is strictly prohibited in periphery so as to secure prompt immune responses.

Keywords: immunoregulatory receptor, T cell differentiation, T cell suppression, tolerance

Transmitting editor: T. Kurosaki

Received 2 March 2009, accepted 24 July 2009.


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