Natural Killer (NK) cell deficiency associated with an epitope-deficient Fc receptor type IIIA (CD16-II).
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.
Jawahar
S
S
Division of Immunology, The Children's Hospital, Boston, MA, USA.
Moody
C
C
Chan
M
M
Finberg
R
R
Geha
R
R
Chatila
T
T
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
D000911:Antibodies, Monoclonal; D000939:Epitopes; D017452:Receptors, IgG