title: Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses.
abstract: 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 T(h) 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.
authors.affiliation: Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Imada
authors.forename: Kyoko
authors.initials: K
authors.lastname: Masuda
authors.forename: Rumi
authors.initials: R
authors.lastname: Satoh
authors.forename: Yumi
authors.initials: Y
authors.lastname: Ito
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Shota
authors.initials: S
authors.lastname: Endo
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
mesh_terms: D000818:Animals; D006087:Graft vs Host Reaction / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D010047:Ovalbumin