From the NIAID at: http://www.niaid.nih.gov/newsroom/re...IVAntibody.htm


Structure of HIV-Neutralizing Antibody Solved

A team of scientists whose leaders are funded by the National Institutes of Health has solved the
structure of an antibody that is able to neutralize HIV, the virus that causes AIDS. Their work is
described in the June 27 issue of "Science".

The antibody, called 2G12, was isolated about a decade ago from one of the rare HIV-positive
individuals whose body is able to successfully combat the virus. Scientists at the Scripps Research
Institute worked with an international team to determine the 2G12 antibody structure by diffracting
X-rays from crystals of 2G12.

The structure reveals an unexpected intertwining of the antibody's two chains, the extensions that
grab hold of the AIDS virus. Researchers also uncovered how the 2G12 antibody neutralizes HIV by
binding to sugars on the surface of the virus. The immune system usually will not attack these
sugars because they are made and attached to the AIDS virus by human cells; the immune system
usually accepts them as if they are part of the body.

Read more, at http://www.niaid.nih.gov/newsroom/re...IVAntibody.htm

On Thu, 3 Jul 2003 20:45:16 +0200, "Alex" <avdeelen.REMOF@wanadoo.nl>
wrote:

Well, first of all, this little blurb is interesting information but
doesn't really mean a lot. Getting anyone else to generate such an
antibody is another task. Whether it has therapeutic use is another
story as MAb? Passive immune therapy? Whether it neutralizes as
effectively as we'd all like to hope to be useful in vaccine design is
unclear....

But after a bit of cold water on this excitement--I find the above
statement to be whack. Antibody recognition of glycosylated sites is
not unknown. Indeed, one of the reasons, aside from hypervariability
in the target, for the failure of the env vaccines (and the stupid
fucks at Vaxgen) was the problem of glycosylation. Stimulating
antibody response to naked env without the sugars is dumb.

Now, I seem to recall reading that there IS recognition of antibodies
to various sugars and/or that they may be displayed along with a
peptide fragment in MHC-II complexes. An article I read a couple years
ago in Immunology Today....so it's not like this is news? Anyway--it's
good to brush up on all this stuff--and dig back into a little deeper
understanding of it.

Technical question. IgG comes in four varieties (IgG1, IgG2, etc.) I
take it this 2G12 means IgG2-12? Doesn't IgG2 have a rather restricted
receptor binding repertoire? I.e., only Fc-gamma-RIIa. Is this
relevant?

It also binds tightly with staph protein A and strep protein
G....lending some credibility to an interesting theory regarding
bacterial load and disease progression...but that's another matter.

Any thoughts?

George M. Carter