Trafficking of major histocompatibility complex class II molecules in human B-lymphoblasts deficient in the AP-3 adaptor complex

Steven H Caplan, Esteban C. Dell'Angelica, William A. Gahl, Juan S. Bonifacino

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The major histocompatibility complex class II subunits (MHC-II) α and β assemble with the invariant chain (Ii) in the endoplasmic reticulum and are transported to endosomal-lysosomal organelles known as MHC class II compartments (MIICs). Although it has been shown that two dileucine-based signals in the cytosolic tail of Ii, as well as a dileucine-based signal in the tail of the β chain mediate sorting to MIICs, the molecular mechanisms by which αβIi complexes are sorted have yet to be resolved fully. The AP-3 adaptor complex stands out as a particularly good candidate for mediating this targeting because: (i) it has a proven role in the trafficking of membrane proteins to lysosome-related organelles; and (ii) it has the ability to interact with dileucine-based signals in vitro. To investigate the potential role of AP-3 in transport of MHC-II to MIICs, we have examined MHC- II trafficking in human B-lymphoblast lines from patients with Hermansky- Pudlak syndrome type 2 (HPS-2), which are deficient in the AP-3 complex. Pulse-chase analyses revealed no significant alteration in the kinetics of synthesis and degradation of either MHC-II subunits or Ii. Moreover, we observed neither impairment of the formation of compact SDS-resistant αβ dimers, nor delay in the appearance of a conformational epitope indicative of a mature, Ii-free αβ dimer. Finally, we demonstrated that in HPS-2 patients' cells, there was no delay in the expression of the αβ dimers on the cell surface. Thus, AP-3 does not seem to be essential for normal trafficking of MHC-II. These findings have important implications for HPS-2 patients, because they suggest that the recurrent bacterial infections suffered by these patients are not likely due to impaired antigen processing and presentation by MHC-II. (C) 2000 Published by Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)113-117
Number of pages5
JournalImmunology Letters
Volume72
Issue number2
DOIs
StatePublished - May 1 2000

Fingerprint

Major Histocompatibility Complex
Antigen Presentation
Organelles
Tail
Human Trafficking
Lysosomes
Bacterial Infections
Endoplasmic Reticulum
Epitopes
Membrane Proteins
Hermansky Pudlak syndrome 2

Keywords

  • Antigen-processing
  • Dileucine-based signals
  • Hermansky-Pudlak syndrome
  • Invariant chain
  • Lysosomes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Trafficking of major histocompatibility complex class II molecules in human B-lymphoblasts deficient in the AP-3 adaptor complex. / Caplan, Steven H; Dell'Angelica, Esteban C.; Gahl, William A.; Bonifacino, Juan S.

In: Immunology Letters, Vol. 72, No. 2, 01.05.2000, p. 113-117.

Research output: Contribution to journalArticle

Caplan, Steven H ; Dell'Angelica, Esteban C. ; Gahl, William A. ; Bonifacino, Juan S. / Trafficking of major histocompatibility complex class II molecules in human B-lymphoblasts deficient in the AP-3 adaptor complex. In: Immunology Letters. 2000 ; Vol. 72, No. 2. pp. 113-117.
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