Factors controlling the trafficking and processing of a leader-derived peptide presented by Qa-1

A. Bai, C. J. Aldrich, J. Forman

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7025-7034
Number of pages10
JournalJournal of Immunology
Volume165
Issue number12
DOIs
StatePublished - Dec 15 2000

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Protein Sorting Signals
Endoplasmic Reticulum
Epitopes
Peptide Hydrolases
Peptides

ASJC Scopus subject areas

  • Immunology

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Factors controlling the trafficking and processing of a leader-derived peptide presented by Qa-1. / Bai, A.; Aldrich, C. J.; Forman, J.

In: Journal of Immunology, Vol. 165, No. 12, 15.12.2000, p. 7025-7034.

Research output: Contribution to journalArticle

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