HLA-DM can partially replace the invariant chain for HLA-DR transport and surface expression in transfected endocrine epithelial cells

The function of HLA class II molecules as peptide presenters to CD4(+) T ce lls depends on the expression of associated molecules such as the invariant chain (Ii) and DM responsible for the correct transport of and high-stabil ity peptide binding to the class II dimers. In organs affected by autoimmun e diseases, endocrine epithelial cells express class II molecules, which pr esumably are involved in the presentation of self-peptides to autoreactive T cells. We have transfected the rat insulinoma cell line RINm5F with diffe rent combinations of HLA-DR, Ii and HLA-DM cDNAs and have studied how Ii an d DM affect the transport and stability of class II molecules expressed by the different transfectants. Immunofluorescence and biochemical analysis sh owed that cells transfected with DR and DM in the absence of Ii expressed m ostly stable molecules in their surface, and showed a lower accumulation of DR molecules in the endoplasmic reticulum (ER) than cells expressing only DR. This suggests that, in the absence of invariant chain, DM molecules can not only exchange peptides other than class II-associated invariant chain peptide (CLIP) but may also be involved in the transport of class II molecu les out of the ER towards the endosomal route. In addition, these data conf irm that expression of DR alone or DR+Ii do not allow the formation of sodi um dodecyl sulphate (SDS)-stable complexes, that cells expressing DR+Ii hav e most DR molecules occupied by CLIP and that Ii and DM molecules allow reg ular routing and peptide loading of class II molecules.