Human immunoglobulin allotypes: previously unrecognized determinants and alleles defined with monoclonal antibodies.

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Abstract
The highly polymorphic system of serologically defined genetic markers on human IgG H chains (Gm allotypes) is second only to the HLA complex in terms of the large number of determinants, alleles and haplotypes that can be used for analyses of disease associations and other genetic studies. Present typing methods are based on the use of anti-Gm antisera that are derived mainly from fortuitously immunized human donors (often requiring processing before use) and must be used in a hemagglutination-inhibition assay that cannot be used in typing for isoallotypic determinants (currently termed non-markers). An allotyping system is described that utilizes monoclonal antibodies in a sandwich modification of the solid-phase radioimmunoassay, which is capable of reliable quantitative typing of allotypic, isoallotypic and isotypic Ig determinants. These highly reproducible, easily disseminated and essentially inexhaustible reagents can be used for rapid, sensitive and quantitative Gm typing. Using this system 2 previously unrecognized Gm determinants were defined, one of which, found to date only in Caucasians, is different from all known Gm markers and defines previously unrecognized alleles and haplotypes. The other determinant cosegregates with the conventional G3m(bl) marker but is distinct from that marker on serological grounds. The successful preparation of mouse monoclonal antibodies that detect human Gm allotypic differences and the development of an assay system capable of typing isoallotypic and allotypic determinants opens the way to further dissection and application of this rich genetic system.