MHC class I molecules are enriched in caveolae but do not enter with simian virus 40

Simian virus 40 (SV40) binds to MHC class I molecules anywhere on the cell surface and then enters through caveolae, The fate of class I molecules after SV40 binding is not known. Sensitivity of I-125-surface-labelled class I molecules to papain cleavage was used to distinguish internalized class I molecules from class I molecules remaining at the cell surface. Whereas the caveolae-enriched membrane microdomain was found to also be enriched for class I molecules, no internalized papain-resistant I-125-surface-labelled class I molecules could be detected at any time in either control cells or in cells preadsorbed with saturating amounts of SV40., Instead, I-125-surface-labelled class I molecules, as well as preadsorbed I-125-labelled anti-class I antibodies, accumulated in the medium, coincident with the turnover of class I molecules at the cell surface. The class I heavy chains that accumulated in the medium were truncated and their release was specifically prevented by the metalloprotease inhibitor 1,10-phenanthroline, Thus, whereas class I molecules mediate SV40 binding, they do not appear to mediate SV40 entry.