Insights into the immunogenetic basis of two ganglioside-associated idiotypic networks.

Abstract:

:The heavy-chain variable regions (VH) from 14F7 MAb, an IgG1 antibody specific for GM3(NeuGc) ganglioside, and its anti-idiotype, the 4G9 MAb, were cloned and sequenced. Comparison with previously reported sequences showed that VH 14F7 belongs to the J558(VHI) gene family and that it is highly mutated. VH 4G9 belongs to the Q52(VHII) gene family. The HCDR3 14F7 sequence contains three basic residues that could be involved in the binding to 4G9 MAb, which bears acidic residues in its HCDR3. Studies performed in the syngeneic model showed that 14F7 MAb requires both coupling to KLH and the use of Freund's adjuvant to induce an effective anti-idiotypic IgG (Ab2) response. In contrast, P3 MAb, a germline gene-encoded Ab1 that also recognizes the GM3(NeuGc) ganglioside through a basic motif in its H-CDRs, has been reported to be immunogenic in syngeneic mice, even when injected in saline. In addition, when Leghorn chickens were immunized with 14F7 or P3 MAbs emulsified in Freund's adjuvant, only P3-immunized animals were able to develop antibodies that recognized NeuGc-containing gangliosides, antigens which are not present in the normal tissues of this animal species. This phenomenon could be due to the lack of idiotypic connectivity of 14F7MAb.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Rodríguez M,Roque-Navarro L,López-Requena A,Moreno E,Mateo de Acosta C,Pérez R,María Vázquez A

doi

10.1016/j.imbio.2006.08.005

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

57-70

issue

1

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(06)00109-4

journal_volume

212

pub_type

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