Functional characterization of a conserved pair of NKR-P1 receptors expressed by NK cells and T lymphocytes in liver and gut.
Natural killer cell receptor protein 1 (NKR-P1) molecules are C-type lectin-like receptors modulating cellular responses toward target cells expressing C-type lectin-like related (Clr) molecules. Although the function of the prototypic rat NKR-P1A receptor and its inhibitory counterpart NKR-P1B are known, little is known about NKR-P1F and NKR-P1G apart from their promiscuity for Clr ligands. Here we generated mAbs against both receptors for phenotypic and functional analyses in rat tissues. NKR-P1F induced redirected lysis and robust Ca(2+) signaling in NK cells, which were prevented by simultaneous engagement of NKR-P1G. NKR-P1G also inhibited NK-cell lysis of Clr transfectants. NKR-P1F was expressed by most NK cells and NKR-P1A(+) T cells in all tissues analyzed, and by many NKR-P1A(-) intestinal T cells, while NKR-P1G was expressed by subsets of these cells with highest prevalence in gut and liver. In the intraepithelial compartment, the proportion of NKR-P1A(+) and NKR-P1F(+) cells was high at birth and thereafter declined, while NKR-P1B(+) and NKR-P1G(+) cells increased with age. Expression levels were also modulated by cytokines, with an increase of NKR-P1B and NKR-P1G induced by inflammatory cytokines, and a reduction of NKR-P1A by TGF-β. The physiological impact of NKR-P1 receptors might thus be dependent on age, tissue, and inflammatory status.
Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Lise
L
Kveberg
Amanda
A
Sudworth
Izabela
I
Todros-Dawda
Marit
M
Inngjerdingen
John T
JT
Vaage
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D006224:Cricetinae; D005786:Gene Expression Regulation; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009928:Organ Specificity; D061251:Primary Cell Culture; D011485:Protein Binding; D051381:Rats; D055647:Rats, Transgenic; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; C560101:Klrb1 protein, rat; C553558:Klrb1a protein, rat; C479632:Klrb1b protein, rat; C560100:Klrb1c protein, rat; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D002118:Calcium
C-type lectin-related molecules; NK-cell receptors; NKR-P1; Rodent