Activity and phenotype of natural killer cells in peptide transporter (TAP)-deficient patients (type I bare lymphocyte syndrome).
In this paper we describe the function and phenotype of natural killer (NK) lymphocytes from HLA class I-deficient patients. These cells are, as has been previously reported, unable to lyse HLA class I- K562 cells, but are able to perform antibody-dependent cellular cytotoxicity (ADCC), although with lower efficiency as compared to NK cells from normal individuals. Transporter associated to antigen processing (TAP)- NK cells proliferate when cultured in the presence of lymphoblastoid B cells (B-LCs) and interleukin 2 and develop a spectrum of cytotoxicity similar to that of activated normal NK cells. Importantly, activation of the TAP- NK cells induces strong cytotoxicity to autologous B-LCs. Analysis of the phenotype of circulating TAP- NK lymphocytes showed them to display a normal diverse repertoire of HLA class I-specific NK receptors. These receptors were expressed at normal levels, apart from the CD94-NKG2A complex, which appeared to be overexpressed. This latter finding could reflect an adaptation to the low expression of HLA class I molecules. Finally, functional analyses indicated that the inhibitory receptors in TAP- individuals can transduce inhibitory signals. Our results suggest that in vivo, the NK cells of TAP- patients could participate in immune defense, at least through ADCC, but upon activation, may be involved in autoimmune processes.
Zimmer
J
J
Laboratoire d'Histocompatibilité, Contrat Jeune Formation Institut National de la Santé et de la Recherche Médicale 94-03, Strasbourg, France.
Donato
L
L
Hanau
D
D
Cazenave
J P
JP
Tongio
M M
MM
Moretta
A
A
de la Salle
H
H
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D017951:Antigen Presentation; D015551:Autoimmunity; D002455:Cell Division; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D011971:Receptors, Immunologic; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse