title: The binding of TAPBPR and Tapasin to MHC class I is mutually exclusive.
abstract: The loading of peptide Ags onto MHC class I molecules is a highly controlled process in which the MHC class I-dedicated chaperone tapasin is a key player. We recently identified a tapasin-related molecule, TAPBPR, as an additional component in the MHC class I Ag-presentation pathway. In this study, we show that the amino acid residues important for tapasin to interact with MHC class I are highly conserved on TAPBPR. We identify specific residues in the N-terminal and C-terminal domains of TAPBPR involved in associating with MHC class I. Furthermore, we demonstrate that residues on MHC class I crucial for its association with tapasin, such as T134, are also essential for its interaction with TAPBPR. Taken together, the data indicate that TAPBPR and tapasin bind in a similar orientation to the same face of MHC class I. In the absence of tapasin, the association of MHC class I with TAPBPR is increased. However, in the absence of TAPBPR, the interaction between MHC class I and tapasin does not increase. In light of our findings, previous data determining the function of tapasin in the MHC class I Ag-processing and presentation pathway must be re-evaluated.
authors.affiliation: Department of Pathology, Cambridge Institute of Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
authors.forename: Clemens
authors.initials: C
authors.lastname: Hermann
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Strittmatter
authors.forename: Janet E
authors.initials: JE
authors.lastname: Deane
authors.forename: Louise H
authors.initials: LH
authors.lastname: Boyle
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D057809:HEK293 Cells; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D015789:HLA-A2 Antigen; D007136:Immunoglobulins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D034741:RNA, Small Interfering; C454688:TAPBPL protein, human; C107762:tapasin