title: Molecular studies and NK cell function of a new case of TAP2 homozygous human deficiency.
abstract: In this paper we describe the clinical and molecular features of a new case (GOR) of homozygous human TAP2 deficiency, analysing the phenotype and function of NK cells. The patient presented from infancy with recurrent sinopulmonary infections; a selective IgG2 deficiency, negative antibody response to polysaccharide vaccination and low level of cell surface expression of HLA class I antigens were found. The sequence of TAP2 gene identified a single mutation, a C to T substitution changing the CGA arg codon at amino acid 220 into TGA stop codon in exon 3. By using MoAbs for KIRs, CD94, CD94/NKG2A and ILT2 we observed, in agreement with others, that the latter two receptors were overexpressed on TAP2-deficient NK cells. The inhibitory CD94/NKG2A and triggering CD94/NKG2C NK receptors, specific for HLA-E, appeared to be functional in a limited number of NK clones that could be expanded in vitro. Expression of HLA-E was virtually undetectable in GOR B-LCL and very faint in PBMC, further supporting that interactions of class I leader sequence nonamers with HLA-E in the ER depend on a functional TAP complex.
authors.affiliation: Servicio de Inmunología, Hospital Universitario Son Dureta, Andrea Doria, Palma de Mallorca, Spain. nmatamoros@hsd.es
authors.forename: N
authors.initials: N
authors.lastname: Matamoros
authors.forename: J
authors.initials: J
authors.lastname: Milà
authors.forename: M
authors.initials: M
authors.lastname: Llano
authors.forename: A
authors.initials: A
authors.lastname: Balas
authors.forename: J L
authors.initials: JL
authors.lastname: Vicario
authors.forename: J
authors.initials: J
authors.lastname: Pons
authors.forename: C
authors.initials: C
authors.lastname: Crespí
authors.forename: N
authors.initials: N
authors.lastname: Martinez
authors.forename: J
authors.initials: J
authors.lastname: Iglesias-Alzueta
authors.forename: M
authors.initials: M
authors.lastname: López-Botet
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D003601:Cytotoxicity Tests, Immunologic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D016130:Immunophenotyping; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000145:classification
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D011506:Proteins; C073119:TAP1 protein, human; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex