A single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite Haemonchus contortus

Sheep immunoglobulin (Ig) heavy-chain (VHDJH) and lambda light-chain variable region (VlJl) nucleotide coding sequence was isolated by reverse transcriptase-polymerase chain reaction (RTPCR) from abomasal lymph node (ALN) B cells of immune sheep challenged with the gastrointestinal nematode parasite...

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Main Authors: White, Greg, Meeusen, E., Newton, S.
Format: Journal Article
Published: ELSEVIER 2001
Online Access:http://hdl.handle.net/20.500.11937/39205
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author White, Greg
Meeusen, E.
Newton, S.
author_facet White, Greg
Meeusen, E.
Newton, S.
author_sort White, Greg
building Curtin Institutional Repository
collection Online Access
description Sheep immunoglobulin (Ig) heavy-chain (VHDJH) and lambda light-chain variable region (VlJl) nucleotide coding sequence was isolated by reverse transcriptase-polymerase chain reaction (RTPCR) from abomasal lymph node (ALN) B cells of immune sheep challenged with the gastrointestinal nematode parasite Haemonchus contortus. Single-chain antibodies (scFv) were then constructed with the purified VHDJH and VlJl Ig gene region DNA using oligonucleotides to PCR and join the variable regions to a central [Gly4Ser]3-linker. In a similar fashion 5'-SfI and 3'-NotI restriction endonuclease sites were added for cloning into a phagemid expression vector. Expression of sheep scFv from pHFA phagemid in an amber-suppresser strain of Escherichia coli, after infection with filamentous phage, resulted in 109 sheep scFv antibodies displayed as a library on phagemid particles. Western blot analysis demonstrated sheep scFv gene expression in E. coli celllysate and on purified library phage. In addition, four rounds of scFv-library selection against H. contortus surface antigen resulted in a 300-fold increase in the elution titre of phage recovered from parasite surface antigen. Nearly 1000 of the selected and eluted scFvs were expressed in an attempt to identify monoclonal sheep scFv against parasite antigen. Only low affinity clones were isolated during screening of this sheep scFv-library, suggesting different strategies will be needed for isolation of specifc high affinity recombinant antibody in future studies.
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publishDate 2001
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spelling curtin-20.500.11937-392052019-02-19T05:35:17Z A single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite Haemonchus contortus White, Greg Meeusen, E. Newton, S. Sheep immunoglobulin (Ig) heavy-chain (VHDJH) and lambda light-chain variable region (VlJl) nucleotide coding sequence was isolated by reverse transcriptase-polymerase chain reaction (RTPCR) from abomasal lymph node (ALN) B cells of immune sheep challenged with the gastrointestinal nematode parasite Haemonchus contortus. Single-chain antibodies (scFv) were then constructed with the purified VHDJH and VlJl Ig gene region DNA using oligonucleotides to PCR and join the variable regions to a central [Gly4Ser]3-linker. In a similar fashion 5'-SfI and 3'-NotI restriction endonuclease sites were added for cloning into a phagemid expression vector. Expression of sheep scFv from pHFA phagemid in an amber-suppresser strain of Escherichia coli, after infection with filamentous phage, resulted in 109 sheep scFv antibodies displayed as a library on phagemid particles. Western blot analysis demonstrated sheep scFv gene expression in E. coli celllysate and on purified library phage. In addition, four rounds of scFv-library selection against H. contortus surface antigen resulted in a 300-fold increase in the elution titre of phage recovered from parasite surface antigen. Nearly 1000 of the selected and eluted scFvs were expressed in an attempt to identify monoclonal sheep scFv against parasite antigen. Only low affinity clones were isolated during screening of this sheep scFv-library, suggesting different strategies will be needed for isolation of specifc high affinity recombinant antibody in future studies. 2001 Journal Article http://hdl.handle.net/20.500.11937/39205 10.1016/S0165-2427(00)00260-9 ELSEVIER restricted
spellingShingle White, Greg
Meeusen, E.
Newton, S.
A single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite Haemonchus contortus
title A single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite Haemonchus contortus
title_full A single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite Haemonchus contortus
title_fullStr A single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite Haemonchus contortus
title_full_unstemmed A single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite Haemonchus contortus
title_short A single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite Haemonchus contortus
title_sort single-chain variable region immunoglobulin library from the abomasal lymph node of sheep infected with the gastrointestinal nematode parasite haemonchus contortus
url http://hdl.handle.net/20.500.11937/39205