RESTRICTED VARIABLE REGION GENE USAGE AND POSSIBLE RHEUMATOID-FACTOR RELATIONSHIP AMONG HUMAN MONOCLONAL-ANTIBODIES SPECIFIC FOR THE AD-1 EPITOPE ON CYTOMEGALOVIRUS GLYCOPROTEIN-B
M. Ohlin et al., RESTRICTED VARIABLE REGION GENE USAGE AND POSSIBLE RHEUMATOID-FACTOR RELATIONSHIP AMONG HUMAN MONOCLONAL-ANTIBODIES SPECIFIC FOR THE AD-1 EPITOPE ON CYTOMEGALOVIRUS GLYCOPROTEIN-B, Molecular immunology, 31(13), 1994, pp. 983-991
The nucleotide sequences of the variable region genes encoding five di
fferent human, high affinity antibodies, specific for the major neutra
lization determinant (AD-1) expressed by human cytomegalovirus glycopr
otein B (gp58/116), have been determined. Three of the five heavy chai
n variable regions belonged to the small VHV-family, although they com
bined with a diverse set of light chains (V(kappa)IIIb, VlambdaII and
VlambdaIII). The other two antibodies belonged to V-H-families III and
IV. One of the VHV-family genes most likely originated from a previou
sly unreported germline gene or allele, since it carries a nine nucleo
tide insert in framework 1. In addition, V-lambda-genes showed variabl
e homology (77-95%) to known germline sequences, while V-kappa-genes s
howed high homology (approximately 98%) with their proposed germline o
rigin. Despite the close homology of the V(kappa)IIIb-gene used to exp
ress one of the antibodies with its corresponding germline gene, the p
rotein did not strongly express some idiotypes associated with this li
ght chain family. There is, thus, no direct relation between the expre
ssion of these crossreactive idiotypes and the use of even modestly mu
tated light chains belonging to this V-kappa-family, which has been im
plicated in the development of anti-idiotypic networks possibly induci
ng autoantibodies, such as rheumatoid factors.