Transfer of GRP94(Gp96)-associated peptides onto endosomal MHC class I molecules

Traffic. 2002 May;3(5):358-66. doi: 10.1034/j.1600-0854.2002.30505.x.

Abstract

GRP94 (gp96)-associated peptides can elicit cellular immune responses, an activity thought to reflect the presence of a cell surface receptor (CD91) on antigen-presenting cells that mediates GRP94 internalization and trafficking to an amenable site for peptide transfer to major histocompatibility complex class I molecules. We report that GRP94 internalized by receptor-mediated endocytosis is trafficked to a Rab5a, CD1 and transferrin-negative, Fc receptor and major histocompatibility complex class I-positive endocytic compartment. Receptor-internalized GRP94 did not access the endoplasmic reticulum of antigen-presenting cells. To identify the site of re-presentation of GRP94-associated peptides, kinetic analyses were performed utilizing GRP94-OVA (SIINFEKL) peptide complexes, with peptide re-presentation assayed with the Kb-SIINFEKL-specific MAb, 25-D1.16. Analyses of the kinetics of re-presentation of GRP94-associated peptides, under conditions in which de novo synthesis of major histocompatibility complex class I molecules was inhibited, identified a post-endoplasmic reticulum compartment, accessed by mature major histocompatibility complex class I, as the predominant site of GRP94-associated peptide exchange onto major histocompatibility complex class I.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Endocytosis
  • Endosomes / metabolism*
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / metabolism*
  • Histocompatibility Antigens Class I / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Peptides / metabolism*

Substances

  • HSP70 Heat-Shock Proteins
  • Histocompatibility Antigens Class I
  • Membrane Proteins
  • Peptides
  • glucose-regulated proteins