The contribution of constant region domains to the binding of murine IgM to Fc mu receptors on T cells.
IgM hybridoma constant region domain deletional mutants were used to investigate the domain requirements for binding of murine IgM to Fc mu receptors (Fc mu R) on normal murine T lymphocytes. Parental Sp 6:18 (mu, kappa; anti-trinitrophenyl) and its mutant proteins or their trinitrophenyl-antigen immune complexes were tested for their ability to inhibit the binding of pentameric IgM to Fc mu R on T lymphocytes. Inhibition was observed with ligands containing multiple copies of the third constant region domain. Inhibition did not occur with ligands missing the third constant region domain. In addition, a battery of rat monoclonal antibodies specific for individual murine IgM constant region domains was tested for the ability to inhibit the binding of pentameric murine IgM to Fc mu R on normal murine T lymphocytes. Total inhibition was observed with the antibodies directed to different epitopes located in C mu 3, but significant inhibition was not observed with antibodies directed to C mu 1, C mu 2, or C mu 4. Studies with domain deletional mutants and anti-domain antibodies have independently provided strong evidence that the C mu 3 domain plays a major role in the binding of IgM to Fc mu R on T lymphocytes and that C mu 1, C mu 2, and C mu 4 are not essential for binding. These studies have also provided evidence that valency and avidity influence the binding of IgM to T lymphocytes that express Fc mu R.
Mathur
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Department of Pathology, University of Iowa, Iowa City 52242.
Lynch
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RG
Köhler
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D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D004252:DNA Mutational Analysis; D007127:Immunoglobulin Constant Regions / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D011961:Receptors, Fc / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007127:Immunoglobulin Constant Regions; D007075:Immunoglobulin M; D046911:Macromolecular Substances; D011961:Receptors, Fc; C035311:immunoglobulin M receptor