PMID: 9530561Apr 8, 1998Paper

Guided selection of antibody fragments specific for human interferon gamma receptor 1 from a human VH- and VL-gene repertoire

Immunotechnology : an International Journal of Immunological Engineering
H WatzkaD Moosmayer

Abstract

The guided selection strategy for isolation of human antibody (Ab) fragments specific for human interferon gamma receptor 1 (IFNGR-1) from a cloned Ab VH and VL repertoire has been investigated. In order to identify recombinant Abs binding to soluble antigen, a novel method termed affinity sedimentation was introduced here. The VH region of murine monoclonal Ab (IR gamma-1) against human IFNGR-1 was combined with human VL repertoire and used for selection of human VL regions. One of these human VL regions (kappa 2) possesses high homology to the murine template VL region, also in CDR3 (77%). A chimeric Fab consisting of kappa 2 and the murine IR gamma-1 VH region was highly IFNGR-1 specific and exerted the same epitope specificity and a comparable binding affinity as the parental murine Fab. In a further step, the selected human VL region kappa 2 was combined with a human VH repertoire and led by guided selection to the generation of a completely human Fab (1b5) specific for human IFNGR-1. The overall VH region homology of 1b5 compared to the parental antibody IR gamma-1 was 81%, with a rather low homology in CDR3. Binding competition studies revealed that the epitope recognized by 1b5 differs from the parental Ab IR gamma-1.

References

Apr 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·H GramA S Kang
Sep 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·C F BarbasS J Benkovic
Dec 21, 1989·Nature·C ChothiaW R Tulip
Mar 24, 1988·Nature·L RiechmannG Winter
Aug 20, 1987·Journal of Molecular Biology·C Chothia, A M Lesk
Dec 5, 1985·Journal of Molecular Biology·C ChothiaM Karplus
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S L MorrisonV T Oi
Apr 1, 1995·Protein Engineering·M ReczkoS Suhai
Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·C F BarbasD R Burton
May 1, 1993·Proteins·T T WuE A Kabat
Apr 1, 1993·Current Opinion in Immunology·M E Goldberg, L Djavadi-Ohaniance
Jun 1, 1996·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·D MoosmayerK Pfizenmaier

❮ Previous
Next ❯

Citations

Aug 1, 2000·Journal of Immunological Methods·Z WangZ Dong
May 17, 2000·The Journal of Clinical Investigation·E JouanguyJ L Casanova
Feb 16, 2005·Expert Opinion on Biological Therapy·Maria A T Groves, Jane K Osbourn
Mar 4, 2008·Journal of Immunological Methods·Hyun-yoo JooSang-hoon Cha
Jul 28, 2004·Journal of Molecular Biology·Monique VogelBeda M Stadler
Apr 26, 2005·Methods : a Companion to Methods in Enzymology·Jane OsbournTristan Vaughan
Dec 18, 2009·Molecular Immunology·Diederik van de WeteringEsther van de Vosse
Apr 6, 2001·International Journal of Cancer. Journal International Du Cancer·M MersmannD Moosmayer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody Specificity

Antibodies produced by B cells are highly specific for antigen as a result of random gene recombination and somatic hypermutation and affinity maturation. As the main effector of the humoral immune system, antibodies can neutralize foreign cells. Find the latest research on antibody specificity here.