Original Article

Cellular and Molecular Life Sciences

, Volume 69, Issue 19, pp 3317-3327

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Direct evidence that the N-terminal extensions of the TAP complex act as autonomous interaction scaffolds for the assembly of the MHC I peptide-loading complex

  • Sabine HulpkeAffiliated withBiocenter, Institute of Biochemistry and Cluster of Excellence Frankfurt (CEF) - Macromolecular Complexes, Goethe-University Frankfurt
  • , Maiko TomiokaAffiliated withLaboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture and Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University
  • , Elisabeth KremmerAffiliated withHelmholtz-Center Munich, German Research Center for Environmental Health, Institute of Molecular Immunology
  • , Kazumitsu UedaAffiliated withLaboratory of Cellular Biochemistry, Division of Applied Life Sciences, Graduate School of Agriculture and Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University
  • , Rupert AbeleAffiliated withBiocenter, Institute of Biochemistry and Cluster of Excellence Frankfurt (CEF) - Macromolecular Complexes, Goethe-University Frankfurt
  • , Robert TampéAffiliated withBiocenter, Institute of Biochemistry and Cluster of Excellence Frankfurt (CEF) - Macromolecular Complexes, Goethe-University Frankfurt Email author 

Abstract

The loading of antigenic peptides onto major histocompatibility complex class I (MHC I) molecules is an essential step in the adaptive immune response against virally or malignantly transformed cells. The ER-resident peptide-loading complex (PLC) consists of the transporter associated with antigen processing (TAP1 and TAP2), assembled with the auxiliary factors tapasin and MHC I. Here, we demonstrated that the N-terminal extension of each TAP subunit represents an autonomous domain, named TMD0, which is correctly targeted to and inserted into the ER membrane. In the absence of coreTAP, each TMD0 recruits tapasin in a 1:1 stoichiometry. Although the TMD0s lack known ER retention/retrieval signals, they are localized to the ER membrane even in tapasin-deficient cells. We conclude that the TMD0s of TAP form autonomous interaction hubs linking antigen translocation into the ER with peptide loading onto MHC I, hence ensuring a major function in the integrity of the antigen-processing machinery.

Keywords

ABC transporter Antigen processing Membrane protein interaction Macromolecular membrane complex Tapasin