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.