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

Li L, Sullivan BA, Aldrich CJ, Soloski MJ, Forman J, Grandea AG, Jensen PE, Van Kaer L
J Immunol. 2004 173 (6): 3707-15

PMID: 15356116 · DOI:10.4049/jimmunol.173.6.3707

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-1b 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 differential 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.

Copyright 2004 The American Association of Immunologists, Inc.

MeSH Terms (25)

Animals Antigen Presentation Antiporters CD8-Positive T-Lymphocytes Cell Differentiation Cell Line Cell Membrane Clone Cells Cytotoxicity, Immunologic H-2 Antigens Histocompatibility Antigens Class I Immunoglobulins Insulin Membrane Transport Proteins Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Peptide Fragments Peptides Protein Sorting Signals Protein Transport Receptors, Antigen, T-Cell T-Lymphocytes, Cytotoxic

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