title: Natural Killer (NK) cell deficiency associated with an epitope-deficient Fc receptor type IIIA (CD16-II).
abstract: Susceptibility to herpes virus infections has been described in experimental animals depleted of NK cells and in patients with defective NK cell function. We have identified a child with recurrent infections, especially with herpes simplex virus, who had a decreased number of CD56(+)CD3(-) NK cells in circulation. Her NK cells expressed an altered form of the Fc receptor for IgG type IIIA (Fc gamma RIIIA or CD16-II) which was not reactive with the anti-CD16-II MoAb B73.1. Sequence analysis revealed the patient to be homozygous for a T to A substitution at position 230 of CD16-II cDNA, predicting a Leu(66) to His(66) change in the first immunoglobulin domain of CD16-II at the B73.1 recognition site. Spontaneous NK cell activity of the patient's peripheral blood mononuclear cells (PBMC) was markedly decreased, while antibody-dependent cellular cytotoxicity (ADCC) was unaffected. These results suggest that this child suffers from a defect affecting the development and function of NK cells, resulting in NK cytopenia and clinically significant immunodeficiency. The role of the CD16-II mutant in the pathogenesis of the patient's NK cell deficiency is discussed.
authors.affiliation: Division of Immunology, The Children's Hospital, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Jawahar
authors.forename: C
authors.initials: C
authors.lastname: Moody
authors.forename: M
authors.initials: M
authors.lastname: Chan
authors.forename: R
authors.initials: R
authors.lastname: Finberg
authors.forename: R
authors.initials: R
authors.lastname: Geha
authors.forename: T
authors.initials: T
authors.lastname: Chatila
mesh_terms: D000911:Antibodies, Monoclonal; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D001483:Base Sequence; D002675:Child, Preschool; D000939:Epitopes / Q000276:immunology; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008969:Molecular Sequence Data; D010033:Otitis Media / Q000276:immunology; D010641:Phenotype; D017452:Receptors, IgG / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D017452:Receptors, IgG