Brief Det~nitive Report Dw/ld-related Molecular Polymorphism of Dr4 Fl-chains*

Antigenic determinants encoded by genes of the HLA-D region have been related to at least three separate molecular complexes, DR, MB (also known as DC and LBE), and SB. At the cell surface each complex has a dimeric structure composed of a structurally conserved a-chain noncovalently associated with a polymorphic fl-chain. The DR and MB series of determinants have been extensively characterized using allospecific serological reagents and, to date, 10 DR and 3 MB allotypes are recognized. Beyond these serologically detectable polymorphisms, HLA-D region products exhibit an additional degree of antigenic complexity revealed by cellular reagents such as homozygous typing cells (HTC). These cells respond to antigenic determinants (Dw/LD determinants) that are phenotypically distinct from those recognized by available antisera. Thus, within a panel of individuals of a single serologically defined DR type, such as DR4, a number of different D w /LD specificities including Dw4, Dwl0, DYT, DB3, and LD40 exist (1). In this report we have addressed this cellularly detected antigenic complexity from a molecular perspective. Using isoelectric focusing (IEF) to analyze DR molecules immunoprecipitated from a panel of individuals homozygous for DR4, but expressing different Dw/LD determinants, we have observed that (a) between DR4 fl-chains, but not a-chains, considerable structural polymorphism exists and (b) the particular DR fl-chain structural configuration observed upon IEF is associated with the cell Dw/LD type. These data, thus, provide the first molecular evidence associating the Dw/LD determinants recognized by cellular reagents to the serologically defined DR molecule.