Identification of NKp80, a novel triggering molecule expressed by   human NK cells.
The ability of NK cells to kill a wide range of tumor or virally infected target cells as well as normal allogeneic T cell blasts appears to depend upon the concerted action of multiple triggering NK receptors. In this study, using two specific monoclonal antibodies [(mAb) MA152 and LAP171], we identified a triggering NK receptor expressed at the cell surface as a dimer of approximately 80 kDa (NKp80). NKp80 is expressed by virtually all fresh or activated NK cells and by a minor subset of T cells characterized by the CD56 surface antigen. NKp80 surface expression was also detected in all CD3- and in 6 / 10 CD3+ large granular lymphocyte expansions derived from patients with lymphoproliferative disease of granular lymphocytes. In polyclonal NK cells, mAb-mediated cross-linking of NKp80 resulted in induction of cytolytic activity and Ca2+ mobilization. A marked heterogeneity existed in the magnitude of the cytolytic responses of different NK cell clones to anti-NKp80 mAb. This heterogeneity correlated with the surface density of NKp46 molecules expressed by different NK clones. The mAb-mediated masking of NKp80 led to a partial inhibition of the NK-mediated lysis of appropriate allogeneic phytohemagglutinin-induced T cell blasts, while it had no effect on the lysis of different tumor target cells, including T cell leukemia cells. These data suggest that NKp80 recognizes a ligand on normal T cells that may be down-regulated during tumor transformation. Molecular cloning of the cDNA coding for NKp80 revealed a type II transmembrane molecule of 231 amino acids identical to the putative protein encoded by a recently identified cDNA termed KLRF1.
Vitale
M
M
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Falco
M
M
Castriconi
R
R
Parolini
S
S
Zambello
R
R
Semenzato
G
G
Biassoni
R
R
Bottino
C
C
Moretta
L
L
Moretta
A
A
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000032:analysis* / Q000235:genetics / Q000502:physiology
D000954:Antigens, Surface; D011971:Receptors, Immunologic; D002118:Calcium