Monensin prevents terminal glycosylation of the N- and O-linked oligosaccharides of the HLA-DR-associated invariant chain and inhibits its dissociation from the alpha-beta chain complex.

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Abstract
In B lymphoblastoid cells, the HLA-DR-associated invariant chain is processed to a form containing O-linked and N-linked oligosaccharides. After neuraminidase treatment, the O-linked carbohydrate is susceptible to digestion with an endoglycosidase (endo-.beta.-N-acetylgalactosaminidase) that cleaves glycans with the structure Gal(.beta.1 .fwdarw. 3)-GalNAc-Ser/Thr, and sialic acid can be added back to this core oligosaccharide by specific sialytransferases. Treatment of cells with the Na ionophore monensin markedly affects the post-translational processing of the invariant chain, although that of associated .alpha. and .beta. chains is minimally affected. Only a small portion of the N-linked carbohydrate on the invariant chain is processed to an endoglycosidase-H-resistant form. The sialic acid residues normally found on the O-linked glycans are not added, but at least the 1st residue, GalNAc, is added. In addition to the changes in glycosylation, an intracellular accumulation of HLA-DR antigens also occurs in monensin-treated cells. The accumulation of HLA-DR antigens and the overall slower turnover rates of the .alpha., .beta. and invariant polypeptides observed after monensin treatment probably reflects the build-up of newly synthesized protiens in Golgi apparatus-derived vacuoles coupled with a decrease in normal degradation in lysosomes.