MOLECULAR CHARACTERIZATION OF A CROSS-REACTIVE IDIOTOPE ON HUMAN-IMMUNOGLOBULINS UTILIZING THE V(H)4-21 GENE SEGMENT

被引:73
作者
POTTER, KN
LI, YC
PASCUAL, V
WILLIAMS, RC
BYRES, LC
SPELLERBERG, M
STEVENSON, FK
CAPRA, JD
机构
[1] UNIV TEXAS,SW MED CTR,DEPT MICROBIOL,DALLAS,TX 75235
[2] SOUTHAMPTON GEN HOSP,TENOVUS RES LAB,LYMPHOMA RES UNIT,SOUTHAMPTON SO9 4XY,HANTS,ENGLAND
[3] UNIV FLORIDA,DEPT MED,DIV RHEUMATOL & CLIN IMMUNOL,GAINESVILLE,FL 32610
关键词
D O I
10.1084/jem.178.4.1419
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The anti-idiotypic (anti-Id) antibody (Ab) 9G4 binds a cross-reactive idiotope (CRI) present in a select group of human autoantibodies. This Id has been localized to the portion of immunoglobulin (Ig) heavy (H) chains encoded by the V(H)4-21 gene segment, a member of the human V(H)4 family. This gene segment is utilized by essentially all cold agglutinin (CA) Abs with I/i specificity isolated from patients with CA disease stemming from chronic lymphoproliferative disorders. In this study, mutational analysis of a CA has been used to determine the structural basis for 9G4 binding to Abs utilizing the V(H)4-21 gene segment. Recombinant CA H chain mutants were produced and their 9G4 reactivity determined. Mutants were generated by exchanging V(H)4-21 sequences in the FRI, CDR1, and CDR2 with corresponding sequences from a closely related gene segment V71-2, a V(H)4 family member that is associated neither with Abs having CA activity nor with Abs that react with 9G4. The results indicate that the motif AVY at amino acid positions 23-25 in FR1 defines the 9G4 idiotope. Reaction of these recombinant Abs with a polyclonal rabbit anti-CA antiserum absorbed to render it specific for a CA CRI also maps predominantly to FR1. These findings indicate that the solvent-exposed FR1 plays an important role in eliciting an immune response to Igs.
引用
收藏
页码:1419 / 1428
页数:10
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