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The Cross‐Reactive Idiotopes Recognized by the Monoclonal Antibodies 9G4 and LCI are Located in Framework Region 1 of Two Non‐Overlapping Subsets of Human VH4 Family Encoded Antibodies
Author(s) -
POTTER K. N.,
LI Y. C.,
CAPRA J. D.
Publication year - 1994
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1994.tb03431.x
Subject(s) - idiotopes , antibody , monoclonal antibody , immunoglobulin light chain , microbiology and biotechnology , idiotype , complementarity determining region , biology , genetics
The monoclonal anti‐idiotopic antibodies LCI and 9G4 bind two non‐overlapping sets of V H 4 encoded antibodies. 9G4 exclusively binds V H 4–21 encoded antibodies, while LCI binds antibodies derived from V H 4 family gene segments V71‐2, V71‐4, V H 4‐18, V H 72‐I and V2‐1. The V H 4–21 gene segment is utilized by most cold agglutinin (CA) antibodies with I/i specificity, while antibodies encoded by other V H 4 gene segments are associated not with CA disease, but primarily with rheumatoid‐factor (RF) activity. We previously determined that the idiotope to which 9G4 binds in V H 4‐21‐derived antibodies is located in framework region l (FR1). In the present study, by using mutational analysis involving individual framework‐ and complementarity‐determining region exchanges between V H 4‐2I‐ and V71‐2‐encoded antibodies, we have found that the idiotope to which LCI binds in V71‐2‐derived antibodies also maps to FR1. The LC1 idiotope is heavy (H)‐chain associated, but requires pairing with a light (L) chain for LCI binding. Recombinant antibodies composed of a variety of kappa (k) and lambda L chains paired with either a V71‐2 or V H 4–21 chain were produced in the baculovirus expression system. LCI bound all of the k‐containing antibodies but did not bind the V71‐2‐encoded H chain alone nor to the two A‐containing antibodies. This experiment demonstrates that not all light chains exert equivalent influence on the conformation of the H‐chain idiotope. These results indicate that the FR1 of V H 4‐encoded antibodies is immunogenic and suggest a physiological role of FR l during an immune response.