Natural Killer (NK) cell deficiency associated with an epitope-deficient Fc receptor type IIIA (CD16-II)

S Jawahar, C Moody, M Chan, R Finberg… - Clinical & …, 1996 - academic.oup.com
S Jawahar, C Moody, M Chan, R Finberg, R Geha, T Chatila
Clinical & Experimental Immunology, 1996academic.oup.com
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 (FcγRIIIA 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 …
Summary
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 (FcγRIIIA 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 Leu66 to His66 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.
Oxford University Press