Class I MHC presentation of exogenous soluble antigen via macropinocytosis in bone marrow macrophages

Christopher C. Norbury (Lead / Corresponding author), Lindsay J. Hewlett, Alan R. Prescott, Nilabh Shastri, Colin Watts

Research output: Contribution to journalArticlepeer-review

333 Citations (Scopus)

Abstract

Extracellular proteins are not generally presented on class 1 MHC molecules in vitro, yet many studies show that a pathway exists in vivo for the presentation of extracellular material on class I molecules to prime CD8+ T cell responses. Here, we provide morphological evidence that proteins taken up by macropinocytosis can gain access to the cytosol and therefore into the conventional class I MHC pathway. Class I presentation of soluble ovalbum in by mouse bone marrow macrophages was dramatically enhanced by MCSF or phorbol ester and blocked by amiloride, which stimulate and inhibit membrane ruffling and macropinocytosis, respectively. Brefeldin A, gelonin, and a peptide aldehyde Inhibitor of proteasomal processing each blocked presentation of macropinocytosed antigen, demonstrating that unusual access to the conventional class 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 soluble proteins, tumor cell fragments, and some pathogens.

Original languageEnglish
Pages (from-to)783-791
Number of pages9
JournalImmunity
Volume3
Issue number6
DOIs
Publication statusPublished - Dec 1995

Fingerprint Dive into the research topics of 'Class I MHC presentation of exogenous soluble antigen via macropinocytosis in bone marrow macrophages'. Together they form a unique fingerprint.

Cite this