Failure of trafficking and antigen presentation by CD1 in AP-3-deficient cells

Immunity. 2002 May;16(5):697-706. doi: 10.1016/s1074-7613(02)00311-4.

Abstract

Endocytosed microbial antigens are primarily delivered to lysosomal compartments where antigen binding to MHC and CD1 molecules occurs in an acidic and proteolytically active environment. Signal-dependent delivery to lysosomes has been suggested for these antigen-presenting molecules, but molecular interactions with vesicular coat proteins and adaptors that direct their lysosomal sorting are poorly understood. Here CD1b but not other CD1 isoforms bound the AP-3 adaptor protein complex. In AP-3-deficient cells derived from patients with Hermansky-Pudlak syndrome type 2 (HPS-2), CD1b failed to efficiently gain access to lysosomes, resulting in a profound defect in antigen presentation. Since MHC class II traffics normally in AP-3-deficient cells, defects in CD1b antigen presentation may account for recurrent bacterial infections in HPS-2 patients.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport
  • Amino Acid Motifs
  • Antigen Presentation*
  • Antigens, Bacterial / immunology
  • Antigens, CD / chemistry
  • Antigens, CD / metabolism
  • Antigens, CD1 / chemistry
  • Antigens, CD1 / metabolism*
  • Antigens, CD1 / physiology*
  • Bacterial Infections / immunology
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Line
  • Gene Deletion
  • Glycoproteins / chemistry
  • Glycoproteins / metabolism
  • HeLa Cells
  • Humans
  • Lipids / immunology
  • Lysosomes / metabolism
  • Lysosomes / ultrastructure
  • Macromolecular Substances
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Monomeric Clathrin Assembly Proteins*
  • Platelet Membrane Glycoproteins / chemistry
  • Platelet Membrane Glycoproteins / metabolism
  • Protein Isoforms / metabolism
  • Protein Transport
  • Syndrome
  • Tetraspanin 30

Substances

  • Adaptor Proteins, Vesicular Transport
  • Antigens, Bacterial
  • Antigens, CD
  • Antigens, CD1
  • CD1C protein, human
  • CD1b antigen
  • CD63 protein, human
  • Carrier Proteins
  • Glycoproteins
  • Lipids
  • Macromolecular Substances
  • Membrane Proteins
  • Monomeric Clathrin Assembly Proteins
  • Platelet Membrane Glycoproteins
  • Protein Isoforms
  • Tetraspanin 30
  • clathrin assembly protein AP180