Re: intracellular staining-phospho specific antibodies

From: Beverly E. Barton (bartonbe@UMDNJ.EDU)
Date: Tue Jul 31 2001 - 07:15:44 EST


Hi Dr. Roy and fellow flowers:
I do this all the time.  I have abandoned Western blot in favor of
intracellular flow cytometry, and I have compared indirect to direct
staining, with similar results.
I use either a biotinylated first step or an unlabeled first step.  If I
use an unlabeled, I use a ligand-affinity-purified polyclonal, and a
labeled F(ab2') for the second step.  I block with Ig of the same
species as the F(ab2').  I have successfully seen p38, STAT3, JAK2, and
a lot of cytokines.  The first step does not have to be one specifically
for flow to work--if it works in westerns and immunohistochemistry
chances are excellent that the Ab will work here too.
A major pitfall is not blocking sufficiently and not washing
sufficiently.  I block with several mg/ml Ig for about 1 hr on ice after
permeabilization.  Also, the first wash after adding Ig, Ab, or second
step must be with buffer added and left there for the same length of
time as the incubation step.  For example, if you left Ab on for 45 min,
you must spin out the Ab and then leave the wash buffer on for 45 min,
then proceed with the subsequent washes as usual.
Another thing I found was that Caltag fix & permeabilization reagents
gave me superior signal to noise ratios for phospho-Ab labeling, while
Pharmingen or home-made reagents gave me very good results for
intracellular cytokines. See these references for more details:
Fleisher et al., Clin Immunol 90:425-430, 1999
Barton & Murphy Cytokine 12:18-27, 2000
Feel free to contact me for more info.
Best,
Beverly Barton
 Assistant Professor
Dept. of Surgery
UMDNJ-New Jersey Medical School

Meenakshi Roy wrote:
>
>   Dear Flow-ers,
>        I recently read the paper "The impact of duration versus extent of
> TCR occupancy on T cell activation: a revision of the kinetic proofreading
> model" by Rosette et al in Immunity Vol 15, July 2001.
>    Here they describe intracellular staining for phospho-Jun and phospho
> MAPK, after T cell activation.
>   I would like to reproduce this.  Has anyone here experience with doing
> this?  What are the pitfalls?  Also, the autohors describe unconjugated
> primary antibodies followed by biton secondary and strep-PE.  Anyone know
> where I can obtain a FITC-conjugated anti-MAPK that would work for this?
>    The clones they use are:
> anti-phospho-p44/p42 MAPK (E10)
> anti-phopspho JNK (G-7)
>
>   What other phospho-antibodies work well for this?
> Regards,
> Dr. Meenakshi Roy
> UCLA



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