Jf. Katz et al., INVARIANT CHAIN AND DM EDIT SELF-PEPTIDE PRESENTATION BY MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-II MOLECULES, The Journal of experimental medicine, 184(5), 1996, pp. 1747-1753
We have studied the consequences of invariant chain (Ii) and DM expres
sion on major histocompatibility complex (MHC) class II function. Ii h
as a number of discrete functions in the biology of class II, includin
g competitive blocking of peptide binding in the endoplasmic reticulum
and enhancing localization in the endocytic compartments. DM is thoug
ht to act primarily in endosomes to promote dissociation of the Ii-der
ived (CLIP) peptide from the class II antigen-binding pocket and subse
quent peptide loading. In this study, we have evaluated the functional
role of Ii and DM by examining their impact on surface expression of
epitopes recognized by a large panel of alloreactive T cells. We find
most epitopes studied are influenced by both Ii and DM. Most strikingl
y, we. find that surface expression of a significant fraction of pepti
de-class II complexes is extinguished, rather than enhanced, by DM exp
ression within the APC. The epitopes antagonized by DM do not appear t
o be specific for CLIP. Finally, we found that DM. was also able to ex
tinguish recognition of a defined peptide derived hom the internally s
ynthesized H-2L(d) protein. Thus, rather than primarily serving in the
removal of CLIP, DM may have a more generalized function of editing t
he array of peptides that are presented by class II. This editing can
be either positive or negative, suggesting that DM plays a specifying
role in the display of peptides presented to CD4 T cells.