Biology Reference
In-Depth Information
UNIQUENESS OF CDRH3
Assuming that the six CDR's can be randomly assorted to generate
antibodies capable of binding various antigens, we would expect that each
specific CDR amino acid sequence would be associated with several
different specificities. This is indeed the case for CDRL1, CDRL2, CDRL3,
CDRH1 and CDRH2. However, a given CDRH3 sequence with five amino
acid residues or more is always associated with a unique specificity (Table
1-3). Several representative amino acid sequences are illustrated here (Wu,
1994).
Table 1-3. Association of certain amino acid sequences of CDR's with different antibody
specificities (modified from Wu, 1994).
CDR
Amino acid sequence
Number of different
specificities
CDRL1
RSSQSLVHSNGNTYLS
16
CDRL2
KVSNRFS
29
CDRL3
SQSTHVPWT
4
CDRH1
DYYMN
10
CDRH2
DINPNNGGTSYNQKFKG
8
CDRH3
YYYGSSLV
1
Since CDRH3 is located in the middle of antibody combining sites, it seems
that this segment of an antibody molecule effectively defines its fine
specificity. In human, CDRH3 can vary from just a few amino acid residues
in length to 31 residues. In cows, camels, etc., it can even be longer. In
mouse, however, the longest CDRH3 is 19 amino acid residues for sequence
so far determined.
Thus, if we want to design an antibody with a special property, we should
start from selecting a CDRH3. Most of them form loop structures, with
about seven or eight amino acid residues giving a more or less flat surface to
the antibody combining site. Shorter ones provide a recessed surface, while
