Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses.
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.
Imada
Michiyo
M
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Masuda
Kyoko
K
Satoh
Rumi
R
Ito
Yumi
Y
Goto
Yoshiyuki
Y
Matsuoka
Takayuki
T
Endo
Shota
S
Nakamura
Akira
A
Kawamoto
Hiroshi
H
Takai
Toshiyuki
T
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
D015395:Histocompatibility Antigens Class I; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D010047:Ovalbumin