Factors controlling the trafficking and processing of a leader-derived peptide presented by Qa-1.
Many leader-derived peptides require TAP for presentation by class I molecules. This TAP dependence can either be ascribed to the inability of proteases resident in the endoplasmic reticulum (ER) to trim leader peptide precursors into the appropriate epitope or the failure of a portion of the leader segment to gain access to the lumen of the ER. Using the Qa-1 binding epitope, Qdm derived from a class Ia leader as a model, we show that many cell types lack ER protease activity to trim this peptide at its C terminus. However, both T1 and T2 cells contain appropriate protease activity to process the full length D(d) leader (DL) when introduced into the ER lumen. Nevertheless, both T1 cells treated with the TAP inhibitor ICP47 and TAP(-) T2 cells fail to present this epitope from either the intact D(d) molecule or a minigene encoding the DL. This indicates that the portion of the leader containing Qdm does not gain access to the ER. However, changing the Arg at P7 of the DL to a Cys can alter its trafficking and allows for TAP-independent presentation of the Qdm epitope.
Bai
A
A
Center for Immunology and Immunology Graduate Program, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Aldrich
C J
CJ
Forman
J
J
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001692:Biological Transport / Q000276:immunology; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D010450:Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D006183:H-2 Antigens / Q000378:metabolism; D006367:HeLa Cells; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D021382:Protein Sorting Signals; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D021382:Protein Sorting Signals; C032907:Q surface antigens; D010450:Endopeptidases