title: Differential requirement for tapasin in the presentation of leader- and insulin-derived peptide antigens to Qa-1b-restricted CTLs.
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-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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: LiQi
authors.initials: L
authors.lastname: Li
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Sullivan
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Aldrich
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Soloski
authors.forename: James
authors.initials: J
authors.lastname: Forman
authors.forename: Andres G
authors.initials: AG
authors.lastname: Grandea
authors.forename: Peter E
authors.initials: PE
authors.lastname: Jensen
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D017920:Antiporters / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007328:Insulin / Q000276:immunology / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000276:immunology; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D017920:Antiporters; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D007328:Insulin; D026901:Membrane Transport Proteins; D010446:Peptide Fragments; D010455:Peptides; D021382:Protein Sorting Signals; C032907:Q surface antigens; C090580:Qdm protein, mouse; D011948:Receptors, Antigen, T-Cell; C107762:tapasin