Re: Some isotypes are stickier than others?

From: Mike Clark (mrc7@mole.bio.cam.ac.uk)
Date: Tue Apr 30 2002 - 11:24:30 EST


On Fri 26 Apr, Karim Vermaelen wrote:
>
> Hello,
> Does anyone know why some mouse Ab isotypes give more background than
> others when staining human cells? We stained single cell suspensions form
> human lung enzymatic digests and have a lot of problems with mouse IgG2a
> antibodies: the isotype control stains very bright. Mouse IgG1 and IgG2b
> are less of a problem... Could someone explain this selective phenomenon
> and/or recommend an optimal blocking strategy to get rid of the problem?
> Thanks a lot, Karim
>

In humans, mice and rats there are multiple IgG subclasses. There are also
multiple classes of FcgR. However in some species such as rabbit there are
no subclasses of IgG.

In those species which have multiple subclasses, different FcgR have
evolved to discriminate different subclasses of IgG. Clearly selection for
this evolutionary adaption takes place within a species not between
species. If you compare the sequences of human IgGs and of human FcgRs with
mouse you will see that both the ligand and the receptor are changing in
sequence.

When you mix IgGs from one species with FcgR bearing cells from another it
is likely that you will see different patterns of cross reactivity.

Rat IgG2b and the related mouse IgG2a seem to react with human FcgR
particularly strongly compared with other rat and mouse subclasses.

see for example

Hale,G., Clark,M., & Waldmann,H. (1985), J. Immunol. 134, 3056-3061
Therapeutic potential of rat monoclonal antibodies: Isotype specificity of
antibody-dependant cell-mediated cytotoxicity with human lymphocytes.

Bruggemann,M., Teale,C., Bindon,C., Clark,M., & Waldmann,H. (1989), J.
Immunol. 142, 3145-3150  A matched set of rat/mouse chimeric antibodies.

Haagen,I-A., Geerars,A.J.G., Clark,M.R., & van de Winkel,J.G.J. (1995),
Journal of Immunology 154, 1852-1860  Interaction of human monocyte Fc
gamma receptors with rat IgG2b: A new indicator for the Fc gamma RIIA
(R-H131) polymorphism


Cheers,

Mike                        <URL:http://www.path.cam.ac.uk/~mrc7/>
--
M.R. Clark, PhD. Division of Immunology
Cambridge University, Dept. Pathology
Tennis Court Rd., Cambridge CB2 1QP
Tel.+44 1223 333705  Fax.+44 1223 333875



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