Biochemical Polymorphism of the DPα and DPβ Chains

The human class II HLA-DP molecules are heterodimers of a 34–36,000 d polypeptide (DPα-chain) noncovalently associated to a 28–29,000 d polypeptide (DPβ-chain) with both the DPα and DPβ chains being encoded by genes located in the most centromeric region of the human major histocompatibility complex (MHC) (1–3). DP molecules, as the other class II molecules DR and DQ, can act as restriction elements for T-cell recognition of foreign antigens (4) and represent important histocompatibility antigens. Although the genetic polymorphism of the DP molecules can be shown by the use of serologic and cellular reagents (5,6), the precise biochemical characterization of the different polymorphic variants has been made difficult by the low levels of expression of these molecules and by their extensive microheterogeneity, particularly that of the DPβ chain. We report here on results of the biochemical analysis of the DPα and DPβ products in 137 individuals from 25 multiplex insulin-dependent diabetes mellitus (IDDM) families which allowed for the direct observation by segregation of the DP molecules encoded by 94 haplotypes. Two DPα and 7 DPβ isoelectric focusing (IEF) variants were characterized. Haplotypic associations between the DP IEF-variants and those of the DR and DQ loci were encountered which suggest a way to discriminate between high and low IDDM risk among otherwise indistinguishable HLA haplotypes.