Critical role for the tapasin-docking site of TAP2 in the functional integrity of the MHC class I-peptide-loading complex

Ralf M Leonhardt; Kirstin Keusekotten; Cemalettin Bekpen; Michael R Knittler

doi:10.4049/jimmunol.175.8.5104

Critical role for the tapasin-docking site of TAP2 in the functional integrity of the MHC class I-peptide-loading complex

J Immunol. 2005 Oct 15;175(8):5104-14. doi: 10.4049/jimmunol.175.8.5104.

Authors

Ralf M Leonhardt¹, Kirstin Keusekotten, Cemalettin Bekpen, Michael R Knittler

Affiliation

¹ University of Cologne, Institute for Genetics, Cologne, Germany.

PMID: 16210614
DOI: 10.4049/jimmunol.175.8.5104

Abstract

The transporter associated with Ag processing (TAP) translocates antigenic peptides into the endoplasmic reticulum for binding onto MHC class I (MHC I) molecules. Tapasin organizes a peptide-loading complex (PLC) by recruiting MHC I and accessory chaperones to the N-terminal regions (N domains) of the TAP subunits TAP1 and TAP2. To investigate the function of the tapasin-docking sites of TAP in MHC I processing, we expressed N-terminally truncated variants of TAP1 and TAP2 in combination with wild-type chains, as fusion proteins or as single subunits. Strikingly, TAP variants lacking the N domain in TAP2, but not in TAP1, build PLCs that fail to generate stable MHC I-peptide complexes. This correlates with a substantially reduced recruitment of accessory chaperones into the PLC demonstrating their important role in the quality control of MHC I loading. However, stable surface expression of MHC I can be rescued in post-endoplasmic reticulum compartments by a proprotein convertase-dependent mechanism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP Binding Cassette Transporter, Subfamily B, Member 3
ATP-Binding Cassette Transporters / genetics
ATP-Binding Cassette Transporters / metabolism
ATP-Binding Cassette Transporters / physiology*
Antiporters / metabolism*
Binding Sites / genetics
Cell Line
Endoplasmic Reticulum / genetics
Endoplasmic Reticulum / metabolism
HLA Antigens / metabolism
HLA Antigens / physiology*
Histocompatibility Antigens Class I / metabolism
Histocompatibility Antigens Class I / physiology*
Humans
Immunoglobulins / metabolism*
Membrane Transport Proteins
Mutation
Peptides / deficiency
Peptides / genetics
Peptides / metabolism*
Protein Transport / genetics

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP Binding Cassette Transporter, Subfamily B, Member 3
ATP-Binding Cassette Transporters
Antiporters
HLA Antigens
Histocompatibility Antigens Class I
Immunoglobulins
Membrane Transport Proteins
Peptides
TAP1 protein, human
tapasin
TAP2 protein, human