Clonal analysis of B- and T-cell responses to Ia antigens. I. Topology of epitope regions on I-Ak and I-Ek molecules analyzed with 35 monoclonal alloantibodies.
Thirty-five Iak-specific monoclonal alloantibodies, derived from hybridomas constructed by fusion between mouse myeloma and spleen cells from A.TH alloimmune mice (Is anti-Ik), have been used to estimate the allotypic polyporphism of the Ik-gene products. Cross-blocking studies using 17 mAb specific for the I-A molecule indicated that six determinants, which were associated with the conventional specificities Ia.2 and Ia.19, were organized in at least three distinct polymorphic areas of the I-Ak molecules. Similarly, another group of six determinants, which did not correspond to previously described conventional Ia specificities, were found to be topologically heterogeneous. By contrast, the five epitopes associated with the Ia. 1 specificity were clustered into a single region of this molecule. In addition the potentiation of binding observed between mAb specific for topologically distinct epitope regions of the I-Ak molecule, suggested that the latter may undergo conformational changes after binding of a given mAb. A similar analysis of 17 mAb specific for the I-Ek molecule indicated that specificity Ia. 7 of the E alpha chain (as defined in this series by eight mAb) was composed of three topologically distinct polymorphic areas, one of which is also spatially related to a complex cluster of eight new determinants of the I-Ek molecule. Finally, one mAb identified a so far undescribed shared determinant of the I-Ak and I-Ek molecules. The present results, which provide a new estimate of the allotypic polymorphism of the Iak antigens, are discussed with regard to their functional, biochemical, and evolutionary implications.
D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006825:Hybridomas / Q000276:immunology*; D007518:Isoantibodies; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D010954:Plasmacytoma; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies