Human NK cells express Fc receptors for IgA which mediate signal transduction and target cell killing.
Receptors for the Fc region of IgG (FcgammaRIIIa, FcgammaRIIc) and IgM (FcmicroR) were previously described on NK cells. In this work the expression of Fc receptors for IgA (FcalphaR) on human NK cells and the signaling events were investigated. The FcalphaR was demonstrated by flow cytometry using secretory IgA (sIgA) and anti-human IgA antibody. The percentage of NK cells (CD3(-)CD56(+)CD16(+)) expressing FcalphaR ranged between 55.7% and 95.7%, with a mean +/- SD of 75.2+/-11.8. The association constant and the number of (125)I-labeled sIgA ((125)I-sIgA) molecules bound per cell, calculated by Scatchard analysis, were 2 x 10(7) M(-1) and 1.7 x 10(4), respectively. The binding specificity was proved by inhibition experiments. Cold sIgA but not IgA Fab fragments were able to inhibit (125)I-sIgA binding in a concentration-dependent manner. Binding of sIgA to NK cells was neither inhibited by anti-mannose receptor antibody, nor by L-fucose, D-galactose, D-glucose, D-mannose or N-acetyl-D-glucosamine. Pretreatment of NK cells with polymeric IgA inhibited their capacity to kill (51)Cr-labeled K562 target cells by 34.8%, whereas with monomeric IgA only by 13.1%. Ligand-induced clustering of the FcalphaR resulted in activation of tyrosine kinases Lck, Syk and phosphatidylinositol 3-kinase. The present studies support the concept that human NK cells bind preferentially sIgA and polymeric IgA with moderate affinity via FcalphaR, which is different from the FcalphaRI/CD89 and other carbohydrate-recognizing receptors like mannose receptor/CD206. This novel structure mediates signal transduction and cell killing.
Mota
Gabriela
G
Center of Immunology, Institute of Virology, Bucharest, Romania.
Manciulea
Mioara
M
Cosma
Ecaterina
E
Popescu
Iulia
I
Hirt
Mirela
M
Jensen-Jarolim
Erika
E
Calugaru
Ana
A
Galatiuc
Cecilia
C
Regalia
Teodor
T
Tamandl
Dietmar
D
Spittler
Andreas
A
Boltz-Nitulescu
George
G
D001665:Binding Sites; D003432:Cross-Linking Reagents; D003602:Cytotoxicity, Immunologic; D004792:Enzyme Precursors / Q000378:metabolism; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D007457:Iodine Radioisotopes; D007694:Killer Cells, Natural / Q000276:immunology*; D007700:Kinetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase
D003432:Cross-Linking Reagents; D004792:Enzyme Precursors; C045281:IgA receptor; D007071:Immunoglobulin A, Secretory; D047908:Intracellular Signaling Peptides and Proteins; D007457:Iodine Radioisotopes; D011961:Receptors, Fc; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C000606896:SYK protein, human; D000072377:Syk Kinase