Clonal analysis of B and T cell responses to Ia antigens. III. Characterization of 12 xenogeneic anti-idiotypic antisera to A.TH-derived anti-I-Ak and anti-I-Ek monoclonal antibodies

Devaux, C.; Pierres, M.

Journal of Immunology 128(2): 751-757

1982


ISSN/ISBN: 0022-1767
PMID: 6172506
Document Number: 182749
The idiotypic diversity of A.TH anti-Iak antibody responses was evaluated by characterizing 12 xenogeneic (rabbit) anti-idiotypic antisera (anti-Id) produced against individual or pools of A.TH-derived mouse anti-I-Ak or anti-I-Ek monoclonal antibodies (mAb). Sensitive cross-idiotype binding assays with 12 anti-Id and 35 125I-labeled A.TH-derived anti-Iak mAb demonstrated that 1 anti-Id bound only its homologous ligand, whereas 11 others detected recurrent idiotypic specificities on their homologous and various heterologous ligands. Each unlabeled homologous ligand was able to inhibit the idiotype binding of the corresponding anti-Id antiserum. In the majority of the anti-Id systems analyzed, no inhibition of homologous idiotype binding was observed with large excess of heterologous ligands. Such discrepancies between cross-idiotype binding and competitive inhibition of idiotype binding assays indicated either recognition by the anti-Id of cross-idiotypic determinants on heterologous ligands with low affinity or the existence of 2 types of anti-Id antibodies in these sera: a dominant one directed at private idiotypic specificities only expressed on the homologous ligand and another detecting recurrent idiotypic specificities on various heterologous ligands. In most of the idiotypic systems analyzed, there was no apparent correlation between the fine antigenic specificities of the various anti-Iak mAb precipitated by a given anti-Id. However, the cross-idiotype binding pattern of three anti-Id suggested a fraction of idiotypic determinants might be shared between some or all of the anti-Ia.1 and anti-Ia.7 mAb, respectively. The binding of radiolabeled anti-Iak mAb to spleen cells could be inhibited by most anti-Id, suggesting the idiotypic determinants recognized by these anti-Id were in proximity of the anti-Iak mAb combining site. The data support the conclusion that A.TH anti-Iak mAb may express individual (IdI) and recurrent (IdX) idiotypic specificities that can be recognized by xenogeneic anti-Id antisera. Such reagents thus represent appropriate probes to analyze the cellular receptors for Ia antigens and the idiotype-anti-Id regulation of allospecific immunity.

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