Tapasin is a 48 kDa glycoprotein which is a
member of the immunoglobulin (Ig) superfamily and it is required
for efficient peptide binding to Transporter associated with Antigen
Processing (TAP). TAP binds peptides in its cytolic part and subsequently
translocates the peptides into the lumen of the endoplasmic reticulum
(ER) where assembly of MHC class I and peptide takes place. Assembly
of MHC class I-ß2-microglobulin (ß2-m) dimers in the
ER involves 2 chaperones, calnexin which interacts with free class
I heavy (H) chains and calreticulin which binds human class I-ß2
dimers prior to peptide loading. Calreticulin remains associated
with at least a subset of class I molecules when they in turn bind
to TAP. Polymorphic differences in MHC class I H chains can result
in quantitative as well as qualitative differences in how they
interact with peptide, ß2-m, calnexin, calreticulin, Erp57,
TAP and Tapasin, a subunit of the TAP complex which binds to both
TAP1 and MHC class I . Data obtained with Tapasin deletion mutants
revealed that binding to TAP is mediated by the C-terminal region
and that the N-terminal region is required to stabilize the MHC
class I loading complex . The Tapasin gene is centromeric of HLA-DP
locus between the HSET and HKE1.5 genes and within 500 kbp of the
transporters associated with antigen processing, TAP1 and TAP2
genes. The localization of these genes within such a short distance
of each other on the chromosome implies some regulatory or functional
significance.
- back - complete
text - |
