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Peptide size selection by the major histocompatibility complex-encoded peptide transporter
F Momburg1, J Roelse, G J Hämmerling
1The Netherlands Cancer Institute, Amsterdam.
The Journal of Experimental Medicine
|May 1, 1994
Summary
The transporter associated with antigen processing (TAP) preferentially imports peptides of 8-11 amino acids into the endoplasmic reticulum for MHC class I binding. Shorter or longer peptides are less efficiently translocated or degraded.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The Major Histocompatibility Complex (MHC)-encoded transporter associated with antigen processing (TAP) is crucial for adaptive immunity.
- TAP facilitates the translocation of cytosolic peptides into the endoplasmic reticulum (ER) for binding to MHC class I molecules.
Purpose of the Study:
- To investigate the peptide length selectivity of TAP-mediated translocation.
- To elucidate the mechanisms governing peptide import into the ER lumen.
Main Methods:
- Utilized streptolysin O-permeabilized cells for studying peptide translocation.
- Employed glycosylatable, radioiodinated model peptides to detect ER lumen import.
- Analyzed peptide transport using directly labeled length variants and TLC.
Main Results:
- TAP-dependent translocation was most efficient for peptides of 9-11 amino acids.
- Peptides shorter than 8 amino acids were inefficiently translocated.
- Short peptides (7-13 amino acids) translocated directly, while longer peptides were clipped by cytosolic peptidases prior to transport.
- Translocated peptides were rapidly released from the ER unless bound to MHC class I or glycosylated.
Conclusions:
- TAP exhibits preferential translocation of peptides with lengths suitable for MHC class I binding.
- Peptide length and subsequent interactions within the ER significantly influence peptide stability and presentation.