Molecular studies and NK cell function of a new case of TAP2 homozygous human deficiency
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.