The majority of H2-M3 is retained intracellularly in a peptide-receptive state and traffics to the cell surface in the presence of N-formylated peptides

Nancy M. Chiu, Taehoon Chun, Miriam Fay, Manas Mandal, Chyung Ru Wang

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

We used a new monoclonal antibody (mAb 130) to analyze the intracellular trafficking and surface expression of H2-M3, the major histocompatibility complex class Ib molecule that presents N-formylated peptides to cytotoxic T cells. M3 surface expression is undetectable in most cell types due to the paucity of endogenous antigen. M3 is induced on the cell surface by addition of high-affinity N-formylated peptides from mitochondria and listeria. Peptide-induced M3 expression is most efficient on antigen presenting cells. Basal and inducible expression of M3 is transporter associated with antigen processing (TAP)-dependent, distinguishing M3 from the class Ib molecules TL and CD1. Unlike the expression of class Ia molecules and a previously described M3/L(d) chimera, surface expression of M3 cannot be rescued by lowered temperature, suggesting that the α3 domain and transmembrane region of M3 may control trafficking. Pulse-chase analysis and use of trafficking inhibitors revealed a pool of empty M3 in the endoplasmic reticulum or early Golgi apparatus. Addition of exogenous peptide allows maturation with kinetics matching those of D(d). The lack of endogenous N-formylated peptide allows discovery of novel pathogen-derived peptides in normal antigen presenting cells. The nonpolymorphic nature of M3 and its ability to present bacterial antigens rapidly and dominantly make it an attractive target for peptide vaccination strategies.

Original languageEnglish
Pages (from-to)423-434
Number of pages12
JournalJournal of Experimental Medicine
Volume190
Issue number3
DOIs
Publication statusPublished - 1999 Aug 2
Externally publishedYes

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Keywords

  • Antigen presentation
  • Cytotoxic T cells
  • Major histocompatibility complex class I
  • N-formylated peptides
  • Rodent

ASJC Scopus subject areas

  • Immunology

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