A new discussion in immunology

Lee Wetzler lwetzler at bu.edu
Wed Jan 26 15:40:42 EST 1994

Shahram Mori (smori at nmsu.edu) wrote:

: Hello Immunetters,
: I came across an article in science Vol 262 pg 844-845 and I wanted to get
: your opinion on it.
: There has been evidence that indicates the presence of a new protein that
: is a costimulator of T-cells.Earlier a protein called B7-1 was involved in
: transmiting a signl needed for the T cell activation. However there  is new
: evidence that indicates a new protein with 26% identity to B7-1. This protein
: was named B7-2. Evidence that B7-1 is not the only stimulatory signal came
: with antibody studies against B7-1 which showed that there was still about 30%
: activation present.Others lines of evidence indicated that mouse with a
: knocked out B7-1 gene also indicated stimulation of Tcells. The evidence
: for B7-2 came from studies involving mice with a knocked out B7-1 gene.
: The Cd-28 receptor ( to which B7-1 binds ) has a related receptor CTLA-4 which
: binds even better than CD-28. When a soluble form of CTLA-4 was given to
: these knocked out mice , there was much surprise because the APC's bound
: the CTLA-4 just as strongly as the normal mice. This was the first real
: evidence of a second Costimulatory signal.
: So there are 2 costimulatory signals B7-1 and B7-2. When they tried to
: find which plays a more important role by looking at the times that B7-1
: and B7-2 appeared on an active APC's surface. They found out that B7-1 did not
: pop up until 24-48 hrs after an APC sent its first signal to the T cell.
: This sounds strange because T- cells need costimulatory signal within 24
: hrs after receiving the first. B7-2 however has mRNA that is present in
: unstimulated APC's. This brings up the question as to what is the function
: of B7-1 if it's not even produced soon enough to stimulate the T-cell?
: Also does the prenesence of an mRNA in ustimulated cells mean that it's
: produced first? It's likely but not certain until one looks at
: translational regulation and Post-translational modification.

: Thanks for responding. I guess posting it is better than e-mailing it so
: that other people can read other's ideas
: Cheers
: Shahram
: 				_/\_
: 			       _\  /_
: 			       \_  _/
: 				 ||

Shahram, much of my work now focuses on B7-2 (by the way, B7-1 is now 
officially CD80) and I have found some bacterial antigens that 
preferentially upregulates B7-2.  The group from Harvard, who I collaborate 
with and who were the authors on two of those papers feel that both antigens 
are important for costimulation that probably B7-2 is more relevant.
Remember much of the in vitro data regarding T lc costimulation has to do 
with cells and transfectants containing B7, so obviously it is involved also. 
I think this demonstrates the morass that immunology truly is.  If there are 
more questions regarding this subject, please email to me.


 ______________________________________  _________________________________
[    Lee Wetzler                       ||                                 ]
[    The Maxwell Finland Laboratory    ||   e-mail  lwetzler at acs.bu.edu   ]
[        for Infectious Diseases       ||                                 ]
[    Boston City Hospital              ||   phone   617-534-4394          ]
[    Boston University                 ||                                 ]
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