RE: MHC-Tetramer Assay

From: Mario Roederer (roederer@drmr.com)
Date: Thu Aug 09 2001 - 20:16:26 EST


Actually, both PE and APC will form larger-order complexes--because
the Streptavidin conjugates of the PBP are often larger-order
complexes (usually, about 3 or 4 SA/PE or SA/PBP per covalent
complex).  The reasons for this are many, including that it is easier
to make than trying to isolate the 1:1 complexes.  However, according
to one manufacturer that I spoke with, their anecdotal evidence is
that people generally "prefer" the preparations of SA-PE (and SA-APC)
that contain these higher-order complexes compared to the 1:1
preparations--primarily because they are brighter than the 1:1
complexes.

We have observed significant differences in brightness between
tetramers made using SA-PE from different manufacurers--presumably
because of the different content of higher-order complexes.

As an aside, the presence of these higher-order complexes means that
comparison of relative brightnesses of any given tetramer reagent on
different samples does not imply that the T cells have different
affinities (or, more properly, avidities) for the MHC-peptide
complex.  Rather, the only way to measure relative avidity is by
doing a titration of the reagent and reporting the concentration that
gives half-maximal fluorescence--a task that is extremely arduous
considering the rarity of these cells.

mr

At 11:55 AM +0200 8/9/01, Voorn, J. wrote:
>Dear Paul,
>
>Perhaps I can not explain the phenomenon you see with the APC conjugates but
>at least I can confirm the same findings with some of our tetramers. We have
>seen that APC sometimes functions better then PE with certain T cell
>populations. We think that it might be due to the difference in size of the
>final constructs, on the other hand it has been suggested that APC form
>larger multimers then 4 (although without evidence).
>I am curious to the experience of other MHC-tetramer users, more information
>on our tetramer facility can be found on our web site www.clb.nl
><http://www.clb.nl>  and go to "reagents".
>
>Best regards,
>
>John
>
>John Voorn				CLB Reagents
>
>
>
>Productmanager			Plesmanlaan 125
>j_voorn@clb.nl <mailto:j_voorn@clb.nl>				1066CX
>AMSTERDAM
>				the Netherlands
>tel  +31-(0)20 5123246
>fax +31-(0)20 5123570			web site www.clb.nl <www.clb.nl>
>
>
>
>	-----Original Message-----
>	From:	PAUL HALLBERG [SMTP:Paul.Hallberg@mail.tju.edu]
>	Sent:	Tuesday, August 07, 2001 5:57 PM
>	To:	Cytometry Mailing List
>	Subject:	MHC-Tetramer Assay
>
>
>	Hi FLOWers,
>
>	Can anyone explain why APC-SA gives a better S/N ratio than PE-SA
>for some
>	MHC Tetramer Assays? In addition, does anyone know an alternative
>	fluorochrome conjugated to strepavidin using 488nm laser excitation?
>
>	Thanks in advance,
>
>	Paul L. Hallberg
>	CORE Flow Cytometry Facility
>	Kimmel Cancer Center
>	Thomas Jefferson University



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