Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment. Export

@article{citeulike:1318727, abstract = {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 VH4-21 gene segment, a member of the human VH4 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 VH4-21 gene segment. Recombinant CA H chain mutants were produced and their 9G4 reactivity determined. Mutants were generated by exchanging VH4-21 sequences in the FR1, CDR1, and CDR2 with corresponding sequences from a closely related gene segment V71-2, a VH4 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.}, address = {Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.}, author = {Potter, K. N. and Li, Y. and Pascual, V. and Williams, R. C. and Byres, L. C. and Spellerberg, M. and Stevenson, F. K. and Capra, J. D.}, citeulike-article-id = {1318727}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/8376944}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=8376944}, day = {1}, issn = {0022-1007}, journal = {J Exp Med}, keywords = {usage, v-gene, vh4-21, vh4-34}, month = {October}, number = {4}, pages = {1419--1428}, posted-at = {2007-05-22 07:06:37}, priority = {2}, title = {Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/8376944}, volume = {178}, year = {1993} }

TY - JOUR ID - citeulike:1318727 L3 - citeulike-article-id:1318727 N2 - 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 VH4-21 gene segment, a member of the human VH4 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 VH4-21 gene segment. Recombinant CA H chain mutants were produced and their 9G4 reactivity determined. Mutants were generated by exchanging VH4-21 sequences in the FR1, CDR1, and CDR2 with corresponding sequences from a closely related gene segment V71-2, a VH4 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. IS - 4 JF - J Exp Med SN - 0022-1007 AD - Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235. EP - 1428 TI - Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment. VL - 178 SP - 1419 KW - usage KW - v-gene KW - vh4-21 KW - vh4-34 AU - Potter, KN AU - Li, Y AU - Pascual, V AU - Williams, RC AU - Byres, LC AU - Spellerberg, M AU - Stevenson, FK AU - Capra, JD PY - 1993/10/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/8376944 ER -