Crucial Role of FcγRIIa (CD32) in Assessment of Functional Anti–Streptococcus pneumoniaeAntibody Activity in Human Sera

0301 basic medicine Immunoglobulin Fab Fragments 03 medical and health sciences Streptococcus pneumoniae Phagocytosis Receptors, IgG Antibody Affinity Leukocytes, Mononuclear Humans Transfection Antibodies, Bacterial 3. Good health
DOI: 10.1086/314603 Publication Date: 2002-07-26T18:58:45Z
ABSTRACT
Immunoglobulin G (IgG)-mediated phagocytosis by polymorphonuclear leukocytes (PMNL) constitutes the main defense against Streptococcus pneumoniae. Two leukocyte IgG receptors, FcgammaRIIa and FcgammaRIIIb, are constitutively expressed on PMNL. Blocking experiments showed FcgammaRIIa is crucial for opsonophagocytosis of serum-opsonized S. pneumoniae. The biallelic, genetically determined FcgammaRIIa polymorphism (FcgammaRIIa-R131 vs. IIa-H131) determines the capacity of IgG2-mediated phagocytosis via this receptor. Comparative studies with PMNL from donors either homozygous for FcgammaRIIa-R131 or IIa-H131 showed the latter had higher phagocytic capacity. These results were confirmed in FcgammaRIIa-R131- and FcgammaRIIa-H131-transfected IIA1.6 cells. The performance of FcgammaRIIa-transfected cells in S. pneumoniae phagocytosis was validated using sera from adults and children. Serum-induced phagocytic activity depended mainly on anti-pneumococcal IgG2 antibodies. Results obtained with PMNL and IIA1.6 cells showed high correlation (r=0.94; P<.001), and support that FcgammaRIIa transfectants are a good alternative to PMNL as effector cells in opsonophagocytosis assays.
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