Biology Reference
In-Depth Information
This uniqueness of CDRH3 sequences, especially at the nucleotide level,
has opened up a powerful method of detecting residual diseases of B cell
lymphomas. The heavy chain variable region nucleotide sequences from
such patients are determined before the initiation of treatment. The CDRH3
sequences are then synthesized and used as probes to detect the existence of
a very small number of malignant cells. Treatment will be continued until
no such cells can be found by this sensitive method. Cross-reaction of the
probe with other heavy chain sequences is usually minimal.
CODING OF CDRH3
Among the above mentioned six CDR's, the coding segment for CDRH3 is
derived completely differently from the other five. Usually, a D-minigene is
first joined to a J-minigene by the process of re-arrangement involving a
number of enzymes (Slackman
et al
., 1996). The joining is not precise, and
intervening nucleotides can be added. Probably two different mechanisms
are involved to incorporate these additional N/P segments. Subsequently,
this D-J segment is then joined to a V-gene, using the same collection of
enzymatic reactions. CDRH3 starts two amino acid residues away from the
second invariant Cys, and ends one residue from the Gly ( ) Gly pair.
According to the Kabat numbering system, CDRH3 is from position 95 to
102, with possible insertions between positions 100 and 101. A schematic
drawing is illustrated in Fig. 1-11.
Figure 1-11
. CDRH3 consists of the 5'-end of V-gene, N/P segment, D-minigene,
another N/P segment, and the 5'-end of J-minigene.