FV-STRUCTURE OF MONOCLONAL-ANTIBODY-II-481 AGAINST HERPES-SIMPLEX VIRUS FC-GAMMA-BINDING GLYCOPROTEIN-GE CONTAINS IMMUNODOMINANT COMPLEMENTARITY-DETERMINING REGION EPITOPES THAT REACT WITH HUMAN-IMMUNOGLOBULIN-M RHEUMATOID FACTORS

Human immunoglobulin M (IgM) rheumatoid factors (RFs) show primary dir ect enzyme-linked immunosorbent assay (ELISA) reactivity with Fab rath er than Fc fragments of monoclonal antibody (mAb) II-481 directed agai nst the Fc gamma-binding site of herpes simplex virus glycoprotein gE. This preferential anti-Fab specificity suggests that RFs react with a ntigen-binding portions of mAb II-481 as anti-idiotypic antibodies dir ected at the combining site regions of mAb reacting with the Fc gamma- binding region of gE. Analysis of this idiotype-anti-idiotype reaction employed polymerase chain reaction amplification and sequencing of th e variable heavy and light (VH and VL) regions of mAb II-481. When VH and VL regions of mAb II-481 were synthesized as overlapping 7-mer pep tides on polypropylene pins, a panel of 10 polyclonal and 6 monoclonal human IgM RFs reacted primarily with epitopes within the three solven t-exposed mAb II-481 complementarity determining regions (CDRs). Prein cubation of single CDR heptamer peptides with IgM RFs in free solution , resulted in 63-100% inhibition of RF binding to mAb II-481 on the EL ISA plate, confirming the antigenic importance of linear CDR regions f or RF reactivity. Combinations of two or three CDR peptides frequently produced 94-100% inhibition of RF binding to whole mAb II-481. Contro l peptides, singly or in combination, showed no inhibition. Computer m odeling suggested that the RF-reactive mAb II-481 Fv region and a prev iously demonstrated RF-reactive CH3 epitope displayed considerable thr ee-dimensional similarities in conformation. These studies may provide insight into limited shape homologies possibly involved in an RF anti -idiotypic reaction.