UNSPECIFIED. (2005) Analysis of a 17-amino acid residue, virus-neutralizing microantibody. JOURNAL OF GENERAL VIROLOGY, 86 (Part 6). pp. 1791-1800. ISSN 0022-1317

Full text not available from this repository.

Abstract

The antibody-binding site, through which an antibody binds to its epitope, is a complex structure formed by the folding together of six complementarity-determining regions (CDRs). However, certain peptides derived from CDR sequences retain antibody specificity and function; these are know as microantibodies (MicroAbs). For example, the F58 MicroAb is a 17 residue, cyclized peptide (CDLIYYDYEEDYYFDYC) derived from CDR-H3 of F58, an IgG1 specific for the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). Both MicroAb and IgG recognize the same epitope in the V3 loop and, despite its small size, the MicroAb neutralizes the infectivity of HIV-1 IIIB only 32-fold less efficiently on a molar basis. The advantage of MicroAbs is that their small size facilitates structure-function analysis. Here, the F58 MicroAlo was investigated using alanine scanning, mass spectroscopy and surface plasmon resonance. Neutralization of infectious IIIB was generally more sensitive to alanine substitution than binding to soluble gp120. There appeared to be a division of function within the MicroAb, with some residues involved in antigen binding (alanine substitution of 11 D, 12Y or 13Y abrogated both binding and neutralization), whereas others were concerned solely with neutralization (substitution of 3L, 8Y or 14F abrogated neutralization, but not binding). The MicroAb is predominantly β-sheet and has strong conformational constraints that are probably essential for activity. The MicroAb and soluble gp120 formed a 1 : 1 complex, with an association rate that was threefold greater than that with IgG and a faster dissociation rate. Its equilibrium dissociation constant is 37.5-fold greater than that of IgG, in line with neutralization data. This study demonstrates how MicroAbs can make a useful contribution to the understanding of antigen-antibody interactions.

Item Type:	Journal Article
Subjects:	T Technology > TP Chemical technology Q Science > QR Microbiology > QR355 Virology
Journal or Publication Title:	JOURNAL OF GENERAL VIROLOGY
Publisher:	SOC GENERAL MICROBIOLOGY
ISSN:	0022-1317
Date:	June 2005
Volume:	86
Number:	Part 6
Number of Pages:	10
Page Range:	pp. 1791-1800
Identification Number:	10.1099/vir.0.80812-0
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/6994

Data sourced from Thomson Reuters' Web of Knowledge

Request changes to a record

Actions (login required)

View Item