Differential requirement for tapasin in the presentation of leader- and insulin-derived peptide antigens to Qa-1b-restricted CTLs

Li Qi Li, Barbara A. Sullivan, Carla J. Aldrich, Mark J. Soloski, James Forman, Andres G. Grandea, Peter E. Jensen, Luc Van Kaer

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The loading of MHC class I molecules with peptides involves a variety of accessory proteins, including TAP-associated glycoprotein (tapasin), which tethers empty MHC class I molecules to the TAP peptide transporter. We have evaluated the role of tapasin for the assembly of peptides with the class Ib molecule Qa-1b. In normal cells, Qa-1b is predominantly bound by a peptide, the Qa-1 determinant modifier (Qdm), derived from the signal sequence of class Ia molecules. Our results show that tapasin links Qa-1 b to the TAP peptide transporter, and that tapasin facilitates the delivery of Qa-1b molecules to the cell surface. Tapasin was also required for the presentation of endogenous Qdm peptides to Qdm-specific, Qa-1b-restricted CTLs. In sharp contrast, tapasin expression was dispensable for the presentation of an insulin peptide to insulin-specific, Qa-1b-restricted CTL isolated from TCR transgenic mice. However, tapasin deficiency significantly impaired the positive selection of these insulin-specific, Qa-1b-restricted transgenic CD8+ T cells. These findings reveal that tapasin plays a dilferential role in the loading of Qdm and insulin peptides onto Qa-1b molecules, and that tapasin is dispensable for retention of empty Qa-1b molecules in the endoplasmic reticulum, and are consistent with the proposed peptide-editing function of tapasin.

Original languageEnglish (US)
Pages (from-to)3707-3715
Number of pages9
JournalJournal of Immunology
Volume173
Issue number6
DOIs
StatePublished - Sep 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Li, L. Q., Sullivan, B. A., Aldrich, C. J., Soloski, M. J., Forman, J., Grandea, A. G., Jensen, P. E., & Van Kaer, L. (2004). Differential requirement for tapasin in the presentation of leader- and insulin-derived peptide antigens to Qa-1b-restricted CTLs. Journal of Immunology, 173(6), 3707-3715. https://doi.org/10.4049/jimmunol.173.6.3707