Sequences of complementary DNAs that encode the NA1 and NA2 forms of Fc receptor III on human neutrophils.

Abstract

Two polymorphic forms of Fc receptor III (FcR III) are expressed on human neutrophils. These differ with respect to their apparent molecular masses after digestion with N-glycanase, and with respect to their reactivity with MAb Gran 11 and alloantisera which recognize determinants (NA1 and NA2) of the biallelic neutrophil antigen (NA) system. To determine the molecular basis for this polymorphism we isolated RNA from neutrophils of NAlNAl and NA2NA2 homozygotes and synthesized corresponding cDNAs. cDNAs encoding FcR III were then amplified using the polymerase chain reaction, cloned, and sequenced. The cDNA that encodes FcR III on NAlNAl neutrophils differed from the cDNA that encodes FcR III on NA2NA2 neutrophils at five nucleotides, predicting four amino acid substitutions. As a result, NA1 FcR III has only four potential N-linked glycosylation sites as compared with six in NA2 FcR III. The amino acid substitutions and differences in the number of potential N-linked glycosylation sites probably account for the different forms of neutrophil FcR III observed after digestion with N-glycanase and for the antigenic heterogeneity of this receptor.

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

“…92 The FcgRIIIb has a biallelic polymorphism, neutrophil antigen 1 (NA1) or 2 (NA2), expressed in polymorphonuclear neutrophils, which are different in four amino acids. 93 Homozygous NA1 individuals have higher IgG-mediated phagocytosis than NA2. 91,93 Fc receptors such as FcgRI, FcgRII, FcgRIII and FcRn show heterogeneous expression patterns in the placenta (Table 2).…”

“…93 Homozygous NA1 individuals have higher IgG-mediated phagocytosis than NA2. 91,93 Fc receptors such as FcgRI, FcgRII, FcgRIII and FcRn show heterogeneous expression patterns in the placenta (Table 2). Immunohistochemical analyses reveal the presence of FcgRI in Hofbauer cells (macrophages) in stromal tissue within the villous; in peripheral monocytes, it mediates endocytosis and degradation of immune complexes, and thus this is probably its function in Hofbauer cells.…”

The genetics of systemic lupus erythematosus: putting the pieces together

“…83,84 These two alleles differ in amino acid sequence and two glycosylation sites. 83,[85][86][87] Individuals who exhibit the Fc␥RIIIB-NA2/NA2 genotype have a decreased capacity to mediate phagocytosis than individuals with the Fc␥RIIIB-NA1/NA1 genotype. 88 Two studies have identified patients who express a rare NA-null allele, leading to a complete absence of the Fc␥RIIIB gene itself.…”

Clonal predominance of CD8+ T cells in patients with unexplained neutropenia

“…The spectrum of antigens implicated in antibody responses in autoimmune neutropenia include NA1, NA2, CD11a and CD11b, CD16, thyrotropin receptor-like molecules and membrane actin-like molecules [31,[34][35][36][37][38][39]. Due to the nature of serological assays, the specificity of the autoantibodies can be more or less precisely established.…”