Class II molecules were isolated from consanguineous HTCs (DR1-DRw8) by sequential immunoprecipitation with the monoclonal antibodies 7.3.19.1 (anti-DRw52-like), B8.11.2 (anti-DR backbone), and 7.5.10.1 (anti-HLA class II backbone). Depending upon the DR-serotype of the cell line used, two or three class II antigen families, distinct in molecular weight, could be isolated (see Hum Immunol 9:221, 1984). Immunoprecipitated class II molecules were treated with NaNase and then analyzed on 1D-IEF gels. Each HLA class II antigen family contained two alpha chains conserved in pI. Furthermore, the various haplotypes show distinct electrophoretic beta chain patterns. The number of beta chain charge configurations detected varies from 2 to 5, depending upon the antigen family or haplotype studied. Some of these chains have a pI which is specific for a given class II serotype whereas other beta chain pIs are invariant and shared among more antigen families or haplotypes.