International Immunology, Vol. 13, No. 1, 23-29,
January 2001
© 2001 Japanese Society for Immunology
Assembly of tapasin-associated MHC class I in the absence of the transporter associated with antigen processing (TAP)
Tumor Immunology, Lund University, Solvegatan 21, 223 62 Lund, Sweden
1 Microbiology and Tumor Biology Center, Karolinska Institute, 171 77 Stockholm, Sweden
Correspondence to: S. Li or P.Wang
The assembly of MHC class I molecules is regulated by a multi-protein complex in the endoplasmic reticules (ER) termed the loading complex. Tapasin is suggested to be one of the molecules forming this complex on the basis of its interaction with both the transporter associated with antigen processing (TAP) and MHC class I molecules. To address whether TAP is indispensable for the processing of the assembly of tapasin-associated MHC class I molecules, we studied the association of MHC class I molecules with tapasin, the assembly of tapasin-associated MHC class I with peptides and the peptide-mediated dissociation of MHC class I from tapasin in TAP-mutant T2 cells. In the absence of TAP, MHC class I heavy chain and ß2-microglobulin dimers were found to be properly associated with tapasin. The stable MHC class I dimer was required for its association with tapasin in the ER. In the absence of TAP, tapasin retained MHC class I molecules much longer in the ER than in the presence of TAP. This low off-rate of MHC class I from tapasin was due to the absence of high-affinity peptides in the ER of TAP-mutant cells but not to the absence of TAP per se. The introduction of peptides into permeabilized microsomes of TAP-mutant cells led to effective loading of the peptides onto tapasin-associated MHC class I and to the subsequent dissociation of MHC class I from tapasin. These results demonstrate that regulation of the assembly of tapasin-associated MHC class I is independent of the interaction of tapasin with TAP, but is dependent upon the peptides transported by TAP.
Keywords: antigenic peptide, MHC, TAP, tapasin
2 Present address: Immunology Group, Department of Pediatric Gastroenterology, St Bartholomew's and the Royal London School of Medicine and Dentistry, Turner Street, London E1 2AD, UK
3 Present address: Department of Biological Science, Brunel University, Uxbridge, Middlesex, UB8 3PH, UK
Transmitting editor: H. Wigzell
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