MEDIATION BY HLA-DM OF DISSOCIATION OF PEPTIDES FROM HLA-DR

HUMAN leukocyte antigen (HLA)-DM is an unconventional major histocompa tibility complex (MHC) class II heterodimer that is important for B-ce ll-mediated antigen processing and presentation to MHC class II-restri cted T cells(1-12). HLA-DM is encoded by two genes, DMA and DMB, which map to the MHC class II region(1), and shares some homology with MHC class I and class II proteins(2,3). Here we define the biochemical rol e of HLA-DM. Recombinant soluble HLA-DM heterodimers have been purifie d from culture supernatants of insect cell transformants. At pH 5.0, t hey induce the dissociation of a subset of peptides bound to HLA-DR, i ncluding a nested set of class-II-associated invariant chain peptides (CLIP). This process liberates HLA-DR and leads to the enhanced bindin g of exogenous peptides.