CLASS-I MHC PRESENTATION OF EXOGENOUS SOLUBLE-ANTIGEN VIA MACROPINOCYTOSIS IN BONE-MARROW MACROPHAGES

Extracellular proteins are not generally presented on class I MHC mole cules in vitro, yet many studies show that a pathway exists in vivo fo r the presentation of extracellular material on class I molecules to p rime CD8(+) T cell responses. Here, we provide morphological evidence that proteins taken up by macropinocytosis can gain access to the cyto sol and therefore into the conventional class I MHC pathway. Class I p resentation of soluble ovalbum in by mouse bone marrow macrophages was dramatically enhanced by MCSF or phorbol ester and blocked by amilori de, which stimulate and inhibit membrane ruffling and macropinocytosis , respectively. Brefeldin A, gelonin, and a peptide aldehyde inhibitor of proteasomal processing each blocked presentation of macropinocytos ed antigen, demonstrating that unusual access to the conventional clas s I MHC pathway was occurring. This novel cell type-specific endocytic pathway may facilitate presentation of exogenous material on class I MHC molecules, allowing induction of CD8(+) T cell responses to solubl e proteins, tumor cell fragments, and some pathogens.