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SELECTING IN SUPPORT OF BIOPHYSICS,
FROM THE MACROMOLECULAR TO SUB ATOMIC AND FUNDAMENTAL PARTICLES. |
Item 1, keywords:
HIV, gp140,
heterogenous,
bivalent
immunoglobulin
binding. | Polyreactivity, disfavoured when B-cells develop from haematoipoetic stem cells (HSC), is observed in three quarters of the 134 unique antibodies to gp140 isolated from 6 HIV infected patients. |
The researchers explored the physiochemical nature of antibodies to HIV at stages from their prespecificity as anti-gp140 antibodies through to their mutated, highly specific nature within virion surface immunogenic complexes. The starting point was the observation that of the 134 gp140 antibodies, 3/4 bound to gp140 via one arm of the immunoglobulin and also via another arm to another site on the virion surface. That heterogenous bivalency in structure is known as polyreactivity.
Only 5 per cent of naive cells (B cells sometimes also called virgin B cells) which have not yet encountered an antigen such as HIV have polyreactive capability and the authors deduce from their physiochemical analysis that the somatic hypermutation which leads to polyreactivity takes place prior to the B cell entering the germinal centre. In other words, they argue first encounter with the HIV triggers hypermutation to a polyreactive immunoglobulin.
The authors reached their conclusion about the timing of hypermutation to polyreactivity by reverting the antibodies' active-domain, protein expression, and they noted that about 70 per cent of antibodies retain or acquire polyreactivity even though affinity to gp140, gained by later hypermutation in the germinal centre, is totally or in significant part lost.
A possible biomolecular advantage of antibody polyreactivity is to make binding possible when the virion surface glycoproteins with which the antibodies ligate are too widely dispersed for homotypic immunoglobulin binding.
Editor's pick of related reading of interest:
http://www.pnas.org/content/107/3/1166.full.pdf+html
Structure of HIV -1 gp120 with gp41- interactive region reveals layered envelope architecture and basis of conformational mobility.
Useful reference reading:
Encyclopaedia of Molecular Biology, Blackwell, 1994, Ed-in-chief Sir John Kendrew.
The above item is based on a paper published in Nature 30.9.10 and was received under embargo by Snippets of science. "Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation", by H. Mouquet et al. Doi:10.1038/nature09385.
Item published in Snippets of science 1.10.10 and minor editing corrections made within a few minutes. |
 Snippets of science, Helen Gavaghan©
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