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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Fingerprint

Glycoproteins
Insulin
Antigens
Peptides
trypsinogen activation peptide
Protein Sorting Signals
Endoplasmic Reticulum
Transgenic Mice
T-Lymphocytes
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Li, L., Sullivan, B. A., Aldrich, C., Soloski, M. J., Forman, J., Grandea, A. G., ... 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.

Differential requirement for tapasin in the presentation of leader- and insulin-derived peptide antigens to Qa-1b-restricted CTLs. / Li, LiQi; Sullivan, Barbara A.; Aldrich, Carla; Soloski, Mark J.; Forman, James; Grandea, Andres G.; Jensen, Peter E.; Van Kaer, Luc.

In: Journal of Immunology, Vol. 173, No. 6, 15.09.2004, p. 3707-3715.

Research output: Contribution to journalArticle

Li, L, Sullivan, BA, Aldrich, C, Soloski, MJ, Forman, J, Grandea, AG, Jensen, PE & 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, vol. 173, no. 6, pp. 3707-3715.
Li, LiQi ; Sullivan, Barbara A. ; Aldrich, Carla ; Soloski, Mark J. ; Forman, James ; Grandea, Andres G. ; Jensen, Peter E. ; Van Kaer, Luc. / Differential requirement for tapasin in the presentation of leader- and insulin-derived peptide antigens to Qa-1b-restricted CTLs. In: Journal of Immunology. 2004 ; Vol. 173, No. 6. pp. 3707-3715.
@article{d6afde3743234883b4d15301507b26bc,
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-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.",
author = "LiQi Li and Sullivan, {Barbara A.} and Carla Aldrich and Soloski, {Mark J.} and James Forman and Grandea, {Andres G.} and Jensen, {Peter E.} and {Van Kaer}, Luc",
year = "2004",
month = "9",
day = "15",
language = "English",
volume = "173",
pages = "3707--3715",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - Differential requirement for tapasin in the presentation of leader- and insulin-derived peptide antigens to Qa-1b-restricted CTLs

AU - Li, LiQi

AU - Sullivan, Barbara A.

AU - Aldrich, Carla

AU - Soloski, Mark J.

AU - Forman, James

AU - Grandea, Andres G.

AU - Jensen, Peter E.

AU - Van Kaer, Luc

PY - 2004/9/15

Y1 - 2004/9/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=4644312290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4644312290&partnerID=8YFLogxK

M3 - Article

C2 - 15356116

AN - SCOPUS:4644312290

VL - 173

SP - 3707

EP - 3715

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -