Abstract Activation of CD8 +T cells against pathogens and cancers involves the recognition antigenic peptides presented in complex with human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA-I proteins is coordinated by a multi-protein called peptide loading (PLC). Tapasin, key PLC component, facilitates optimization peptides. However, different allotypes have variable requireme...

Abstract T cell immunity to viruses and cancers is crucially dependent on the surface display of major histocompatibility complex class I (MHC-I) molecules selectively loaded with high affinity peptides. Peptide loading occurs in ER within a multimolecular assembly known as peptide (PLC). A critical component PLC tapasin, 45 kDa membrane glycoprotein whose absence expression stability MHC-I are...

For their efficient assembly in the endoplasmic reticulum (ER), major histocompatibility complex (MHC) class I molecules require the specific assembly factors transporter associated with antigen processing (TAP) and tapasin, as well as generic ER folding factors, including the oxidoreductases ERp57 and protein disulfide isomerase (PDI), and the chaperone calreticulin. TAP transports peptides fr...

Cell surface expression of MHC I molecules depends on the chaperone tapasin; how tapasin functions is not fully understood. We created three fluorescent tapasin constructs: wild-type tapasin, soluble tapasin, which does not interact with TAP, and N300 tapasin, which does not interact with MHC I. In contrast to earlier reports, all three constructs localize to the endoplasmic reticulum (ER), tho...

Tapasin influences the quantity and quality of MHC/peptide complexes at the cell surface; however, little is understood about the structural features that underlie its effects. Because tapasin, MHC class I, and TAP are transmembrane proteins, the tapasin transmembrane/cytoplasmic region has the potential to affect interactions at the endoplasmic reticulum membrane. In this study, we have assess...

Tapasin edits the peptide repertoire presented to CD8(+) T cells by favoring loading of slow off-rate peptides on MHC I molecules. To investigate the role of tapasin on T cell immunodominance we used poxvirus viral vectors expressing a polytope of lymphocytic choriomeningitis virus epitopes with different off-rates. In tapasin-deficient mice, responses to subdominant fast off-rate peptides were...

Tapasin is critical for efficient loading and surface expression of most HLA class I molecules. The high level surface expression of HLA-B*2705 on tapasin-deficient 721.220 cells allowed the influence of this chaperone on peptide repertoire to be examined. Comparison of peptides bound to HLA-B*2705 expressed on tapasin-deficient and -proficient cells by mass spectrometry revealed an overall red...

The Major Histocompatibility Complex (MHC) is one of the most gene dense regions in the genome and studies in several species have shown significant associations between the MHC and disease. The endoplasmic reticular glycoprotein, tapasin, is involved in the MHC class I antigen presentation pathway. Sheep TAPASIN is located in the class IIb region of the MHC. Sheep TAPASIN was subcloned from BA...

Different HLA class I alleles display a distinctive dependence on tapasin for surface expression and Ag presentation. In this study, we show that the tapasin dependence of HLA class I alleles correlates to the nature of the amino acid residues present at the naturally polymorphic position 114. The tapasin dependence of HLA class I alleles bearing different residues at position 114 decreases in ...

Tapasin has been shown to stabilize TAP and to link TAP to the MHC class I H chain. Evidence also has been presented that tapasin influences the loading of peptides onto MHC class I. To explore the relationship between the ability of tapasin to bind to TAP and the MHC class I H chain and the ability of tapasin to facilitate class I assembly, we have created novel tapasin mutants and expressed t...