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Residues in TAP2 peptide transporters controlling substrate specificity
F Momburg1, E A Armandola, M Post
1Department of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Journal of Immunology (Baltimore, Md. : 1950)
|March 1, 1996
Summary
The transporter associated with antigen processing (TAP) moves peptides for MHC class I. Researchers identified specific residues in rat TAP2 that control peptide transport specificity, differing between rat alleles.
Area of Science:
- Immunology
- Molecular Biology
- Protein Transport
Background:
- The transporter associated with antigen processing (TAP) is crucial for presenting peptides to MHC class I molecules.
- TAP facilitates the translocation of peptides from the cytosol into the endoplasmic reticulum.
- Previous studies indicated differential C-terminal peptide residue specificity among TAP alleles.
Purpose of the Study:
- To identify the molecular basis for differential peptide transport specificity in rat TAP alleles.
- To map the specific regions within rat TAP2 responsible for observed transport differences.
Main Methods:
- Construction of hybrid rat TAP2 alleles by combining rat TAP2a and TAP2u.
- Co-expression of hybrid rat TAP2 with rat TAP1 in TAP-deficient T2 cells.
- Analysis of peptide transport specificity using the constructed TAP variants.
Main Results:
- Two distinct regions within rat TAP2 were identified as critical for differential peptide transport.
- Each critical region contains two polymorphic residues that dictate substrate specificity.
- These key residues are located in putative cytoplasmic loops near the membrane.
Conclusions:
- Specific polymorphic residues in rat TAP2 control the differential C-terminal peptide transport specificity.
- These findings elucidate the molecular determinants of TAP allele-specific peptide selection.
- Understanding these mechanisms is vital for comprehending antigen presentation pathways.