Structure of human immunoglobulin gamma genes: implications for evolution of a gene family

Takahashi, Nobutaka; Ueda, Shintaroh; Obata, Masahiro; Nikaido, Toshio; Nakai, S.; Honjo, Tasuku

doi:10.1016/0092-8674(82)90183-0

Cited by 220 publications

(106 citation statements)

References 34 publications

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“…Briefly, substitutions of C 1348 3 G, G 1356 3 T, and C 1359 3 T according to the numbering system of ref. 35 were introduced by using the Bsa I site at position 1334 near the C terminus of CH 2 of IgG 1A5 to generate IgG 1A5 ⌬A containing amino acid substitutions at 327, 330, and 331 according to the numbering system of ref. 17.…”

Section: Methodsmentioning

confidence: 99%

Monoclonal antibody-mediated enhancement of dengue virus infectionin vitroandin vivoand strategies for prevention

Goncalvez

Engle

Claire

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

340

292

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antibody-dependent enhancement ͉ nonhuman primate model ͉ Fc mutations ͉ cross-reactive mAb T he four dengue virus (DENV) serotypes (DENV-1 to DENV-4) are the most important arthropod-borne flaviviruses in terms of morbidity and geographic distribution. Up to 100 million DENV infections occur every year, mostly in tropical and subtropical areas where vector mosquitoes are abundant (1). Infection with any of the DENV serotypes may be asymptomatic or may lead to classic dengue fever or more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which are increasingly common in the dengue endemic areas. Immunity to the same virus serotype (homotypic immunity) is life-long, whereas immunity to different serotypes (heterotypic immunity) lasts 2-3 months so that infection with a different serotype virus is possible (2). DHF/DSS often occurs in patients with second, heterotypic DENV infections or in infants with maternally transferred dengue immunity (3, 4). Severe dengue is a major cause of hospitalization, and fatality rates vary from Ͻ1% to 5% in children.Antibody-dependent enhancement (ADE) has been proposed as an underlying pathogenic mechanism of DHF/DSS (3). ADE occurs because preexisting subneutralizing antibodies and the infecting DENV form complexes that bind to Fc receptorbearing cells, leading to increased virus uptake and replication (4). ADE has been repeatedly demonstrated in vitro using dengue immune sera or monoclonal antibodies and cells of monocytic and recently, B lymphocytic lineages bearing Fc receptors (5-7). ADE of DENV-2 infection has also been demonstrated in monkeys infused with a human dengue immune serum (8).Infection with DENV or any other flavivirus induces broadly cross-reactive but weak or nonneutralizing antibodies (9, 10). These antibodies remain detectable for a long period and rise rapidly during a subsequent heterotypic infection as a result of an anamnestic response. A major subset of these cross-reactive antibodies is directed to immuno-dominant epitopes involving determinants mapped to the flavivirus-conserved fusion peptide in the envelope glycoprotein (E) (11-13). The functional activities of these cross-reactive antibodies are not well characterized.We have identified chimpanzee-human chimeric IgG1 mAbs capable of neutralizing or binding to one or more DENV serotypes (14, 15). Cross-reactive IgG 1A5 neutralizes DENV-1 and DENV-2 more efficiently than DENV-3 and DENV-4, and type-specific IgG 5H2 neutralizes DENV-4 at a high titer (14,15). Analysis of antigenic variants has localized the IgG 1A5 binding site to the conserved fusion peptide in E (11). Thus, IgG 1A5 shares many characteristics with the cross-reactive antibodies detected in flavivirus infections.We investigated the ability of IgG 1A5 to mediate enhancement of DENV replication in monocyte-derived cell lines and in juvenile rhesus monkeys after passive transfer. We also explored strategies to reduce ADE by mutational analysis of the key structures in the Fc of IgG 1A5. A 9-aa deletion at the N termin...

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Section: Methodsmentioning

confidence: 99%

Monoclonal antibody-mediated enhancement of dengue virus infectionin vitroandin vivoand strategies for prevention

Goncalvez

Engle

Claire

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

340

292

View full text Add to dashboard Cite

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“…␥1R, ␥3R, and ␥4R were designed from the unique C␥1, C␥3, and C␥4 hinge regions (26) (exon II) (Table II). Different ␥ genes share Ͻ60% homology in the hinge region (26). The orientation of the primers ensures that the amplified CT are from the excised switch circle and not from the rearranged genomic DNA.…”

Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

“…Primer C␥R is derived from the published sequence of the first C␥ exon that is identical between subclasses (25,26). Such I⑀-C␥ CT could be generated either by an earlier direct or sequential switch from to one or more ␥ genes (Fig.…”

Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis

Takhar

Smurthwaite

Coker

et al. 2005

The Journal of Immunology

198

187

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IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and ε circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and ε circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.

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“…Our results identified several upregulated genes including IL-1R2, an IL-1R that antagonizes IL-1-mediated events (28), and MRP-14, a calcium-binding protein expressed during chronic inflammation (29). Several genes that have not been previously linked to UC, such as HBG2 (30), galectin 3 (31), and immunoglobulin heavy constant γ3 (32), were also upregulated. The widespread upregulation of these genes involved in receptor (IL-1R2), metal (MRP-14), energy/metabolism (HBG2), serum protein/anti-coagulation (galectin 3), and cell surface antigen/immune (immunoglobulin heavy constant γ3) processes may indicate a major disruption in cellular homeostasis in UC.…”

Section: Discussionmentioning

confidence: 68%

Microarray analyses of peripheral whole blood cells from ulcerative colitis patients: Effects of leukocytapheresis

Kobayashi

Mitsuyama

Yamasaki

et al. 2013

International Journal of Molecular Medicine

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Abstract.Complementary DNA microarray technology allows the simultaneous analysis of the expression of hundreds to thousands of genes. We applied this technique to clarify the molecular mechanisms underlying the therapeutic effects of leukocytapheresis (LCAP) therapy in patients with ulcerative colitis (UC). A 776-gene microarray analysis was performed using whole blood cells from six normal subjects and six patients with active UC who had undergone filtration LCAP. Widespread gene upregulation was observed in patients with UC, compared with normal subjects. After LCAP, genes with proinflammatory actions, such as CD97, CD74, human leukocyte antigen-DRβ1 and -DP light chain, were downregulated, while genes responsible for antimicrobial actions, such as neutrophil gelatinase-associated lipocalin, and acute phase reactions, such as haptoglobin α1S and α1-acid glycoprotein, were upregulated. In conclusion, we identified several genes expressed in the whole blood cells of UC patients as well as the transcriptional events following LCAP. Following LCAP, the gene profile shifted toward a pattern indicating disease improvement. These results suggest a basis for the molecular mechanisms leading to the therapeutic effects of LCAP and also indicate new therapeutic targets, providing important prognostic information.

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Structure of human immunoglobulin gamma genes: implications for evolution of a gene family

Cited by 220 publications

References 34 publications

Monoclonal antibody-mediated enhancement of dengue virus infectionin vitroandin vivoand strategies for prevention

Monoclonal antibody-mediated enhancement of dengue virus infectionin vitroandin vivoand strategies for prevention

Allergen Drives Class Switching to IgE in the Nasal Mucosa in Allergic Rhinitis

Microarray analyses of peripheral whole blood cells from ulcerative colitis patients: Effects of leukocytapheresis

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