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Weissenhorn, Winfried; Cheng, Y. H.; Riethmüller, Gert; Rieber, Ernst Peter; Weiss, Elisabeth H.
(1992):
VH-RELATED IDIOTOPES DETECTED BY SITE-DIRECTED MUTAGENESIS. A Study Induced by the Failure to Find CD4 Anti-Idiotypic AntibodieMs imicking the Cellular Receptor of HIV.
In: Journal of Immunology, Vol. 149: pp. 1237-1241
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![[img]](https://epub.ub.uni-muenchen.de/3022/1.hassmallThumbnailVersion/012.pdf)  Preview |
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Abstract
The function of the CD4 cell surface protein as
coreceptor on T helper lymphocytes and as receptor
for HIV makes this glycoprotein a prime target for
an immune intervention with mAb. A detailed understanding
of the structural determinants on the
therapeutic CD4 mAb that are involved in Ag binding
or are recognized by anti-idiotypic mAb (anti-Id)
may be important for designing antibodies with optimal
therapeutic efficacy. Seven anti-Id raised
against the CD4 mAb M-T310 were selected from a
large panel with the intention to obtain CD4 mimicking
structures with specificity foHr IV gp120. The
selected anti-Id did not reacwt ith other CDCspecific
mAb cross-blocking M-T310. Among these, mAb MT404,
although having the same L chain as M-T310
and a VH region sequence differing onlya t 14 amino
acid positions, was not recognized by the anti-Id. MT310
H chain complexed with the J558L L chain
reacted with all anti-Id, thus demonstrating that the
recognized idiotopes are located within the VH region.
To identify the idiotopes of M-T310 seen by
the anti-Id, variants of M-T404 containing one or
more of the M-T3 1 O-derived substitutions were generated
by oligonucleotide-directed mutagenesis.
The reactivity pattern of the mutant proteins with
the anti-Id demonstrated that the idiotopes reside
within the complementarity determining region
(CDR) 2 and CDR3 loops of the VH region. A major
idiotope was definebdy a single amino acid in CDR2
that was recognized by three anti-Id, whereas the
four other anti-Id reacted with determinants of
CDR3. Although the performed amino acid substitutions
did influence the Id recognition, Ag binding
was not significantly affected, suggesting that none
of the anti-Id can be considered as a mimicry of the
CD4 Ag
