Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain α3 domain

Woong Kyung Suh, Michael A. Derby, Myrna F. Cohen-Doyle, Gary J. Schoenhals, Klaus Frueh, Jay A. Berzofsky, David B. Williams

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

In human cells the association of MHC class I molecules with TAP is thought to be mediated by a third protein termed tapasin. We now show that tapasin is present in murine TAP-class I complexes as well. Furthermore, we demonstrate that a mutant H-2D(d) molecule that does not interact with TAP due to a Glu to Lys mutation at residue 222 of the H chain (D(d)(E222K)) also fails to bind to tapasin. This finding supports the view that tapasin bridges the association between class I and TAP and implicates residue 222 as a site of contact with tapasin. The inability of D(d)(E222K) to interact with tapasin and TAP results in impaired peptide loading within the endoplasmic reticulum. However, significant acquisition of peptides can still be detected as assessed by the decay kinetics of cell surface D(d)(E222K) molecules and by the finding that prolonged viral infection accumulates sufficient target structures to stimulate T cells at 50% the level observed with wild-type D(d). Thus, although interaction with tapasin and TAP enhances peptide loading, it is not essential. Finally, a cohort of D(d)(E222K) molecules decays more rapidly on the cell surface compared with wild-type D(d) molecules but much more slowly than peptide-deficient molecules. This suggests that some of the peptides obtained in the absence of an interaction with tapasin and TAP are suboptimal, suggesting a peptide-editing function for tapasin/TAP in addition to their role in enhancing peptide loading.

Original languageEnglish (US)
Pages (from-to)1530-1540
Number of pages11
JournalJournal of Immunology
Volume162
Issue number3
StatePublished - Feb 1 1999
Externally publishedYes

Fingerprint

trypsinogen activation peptide
Peptides
tapasin
Virus Diseases

ASJC Scopus subject areas

  • Immunology

Cite this

Suh, W. K., Derby, M. A., Cohen-Doyle, M. F., Schoenhals, G. J., Frueh, K., Berzofsky, J. A., & Williams, D. B. (1999). Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain α3 domain. Journal of Immunology, 162(3), 1530-1540.

Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain α3 domain. / Suh, Woong Kyung; Derby, Michael A.; Cohen-Doyle, Myrna F.; Schoenhals, Gary J.; Frueh, Klaus; Berzofsky, Jay A.; Williams, David B.

In: Journal of Immunology, Vol. 162, No. 3, 01.02.1999, p. 1530-1540.

Research output: Contribution to journalArticle

Suh, WK, Derby, MA, Cohen-Doyle, MF, Schoenhals, GJ, Frueh, K, Berzofsky, JA & Williams, DB 1999, 'Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain α3 domain', Journal of Immunology, vol. 162, no. 3, pp. 1530-1540.
Suh, Woong Kyung ; Derby, Michael A. ; Cohen-Doyle, Myrna F. ; Schoenhals, Gary J. ; Frueh, Klaus ; Berzofsky, Jay A. ; Williams, David B. / Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain α3 domain. In: Journal of Immunology. 1999 ; Vol. 162, No. 3. pp. 1530-1540.
@article{fdb00d7b4cec4343910f98682fab2b7a,
title = "Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain α3 domain",
abstract = "In human cells the association of MHC class I molecules with TAP is thought to be mediated by a third protein termed tapasin. We now show that tapasin is present in murine TAP-class I complexes as well. Furthermore, we demonstrate that a mutant H-2D(d) molecule that does not interact with TAP due to a Glu to Lys mutation at residue 222 of the H chain (D(d)(E222K)) also fails to bind to tapasin. This finding supports the view that tapasin bridges the association between class I and TAP and implicates residue 222 as a site of contact with tapasin. The inability of D(d)(E222K) to interact with tapasin and TAP results in impaired peptide loading within the endoplasmic reticulum. However, significant acquisition of peptides can still be detected as assessed by the decay kinetics of cell surface D(d)(E222K) molecules and by the finding that prolonged viral infection accumulates sufficient target structures to stimulate T cells at 50{\%} the level observed with wild-type D(d). Thus, although interaction with tapasin and TAP enhances peptide loading, it is not essential. Finally, a cohort of D(d)(E222K) molecules decays more rapidly on the cell surface compared with wild-type D(d) molecules but much more slowly than peptide-deficient molecules. This suggests that some of the peptides obtained in the absence of an interaction with tapasin and TAP are suboptimal, suggesting a peptide-editing function for tapasin/TAP in addition to their role in enhancing peptide loading.",
author = "Suh, {Woong Kyung} and Derby, {Michael A.} and Cohen-Doyle, {Myrna F.} and Schoenhals, {Gary J.} and Klaus Frueh and Berzofsky, {Jay A.} and Williams, {David B.}",
year = "1999",
month = "2",
day = "1",
language = "English (US)",
volume = "162",
pages = "1530--1540",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "3",

}

TY - JOUR

T1 - Interaction of murine MHC class I molecules with tapasin and TAP enhances peptide loading and involves the heavy chain α3 domain

AU - Suh, Woong Kyung

AU - Derby, Michael A.

AU - Cohen-Doyle, Myrna F.

AU - Schoenhals, Gary J.

AU - Frueh, Klaus

AU - Berzofsky, Jay A.

AU - Williams, David B.

PY - 1999/2/1

Y1 - 1999/2/1

N2 - In human cells the association of MHC class I molecules with TAP is thought to be mediated by a third protein termed tapasin. We now show that tapasin is present in murine TAP-class I complexes as well. Furthermore, we demonstrate that a mutant H-2D(d) molecule that does not interact with TAP due to a Glu to Lys mutation at residue 222 of the H chain (D(d)(E222K)) also fails to bind to tapasin. This finding supports the view that tapasin bridges the association between class I and TAP and implicates residue 222 as a site of contact with tapasin. The inability of D(d)(E222K) to interact with tapasin and TAP results in impaired peptide loading within the endoplasmic reticulum. However, significant acquisition of peptides can still be detected as assessed by the decay kinetics of cell surface D(d)(E222K) molecules and by the finding that prolonged viral infection accumulates sufficient target structures to stimulate T cells at 50% the level observed with wild-type D(d). Thus, although interaction with tapasin and TAP enhances peptide loading, it is not essential. Finally, a cohort of D(d)(E222K) molecules decays more rapidly on the cell surface compared with wild-type D(d) molecules but much more slowly than peptide-deficient molecules. This suggests that some of the peptides obtained in the absence of an interaction with tapasin and TAP are suboptimal, suggesting a peptide-editing function for tapasin/TAP in addition to their role in enhancing peptide loading.

AB - In human cells the association of MHC class I molecules with TAP is thought to be mediated by a third protein termed tapasin. We now show that tapasin is present in murine TAP-class I complexes as well. Furthermore, we demonstrate that a mutant H-2D(d) molecule that does not interact with TAP due to a Glu to Lys mutation at residue 222 of the H chain (D(d)(E222K)) also fails to bind to tapasin. This finding supports the view that tapasin bridges the association between class I and TAP and implicates residue 222 as a site of contact with tapasin. The inability of D(d)(E222K) to interact with tapasin and TAP results in impaired peptide loading within the endoplasmic reticulum. However, significant acquisition of peptides can still be detected as assessed by the decay kinetics of cell surface D(d)(E222K) molecules and by the finding that prolonged viral infection accumulates sufficient target structures to stimulate T cells at 50% the level observed with wild-type D(d). Thus, although interaction with tapasin and TAP enhances peptide loading, it is not essential. Finally, a cohort of D(d)(E222K) molecules decays more rapidly on the cell surface compared with wild-type D(d) molecules but much more slowly than peptide-deficient molecules. This suggests that some of the peptides obtained in the absence of an interaction with tapasin and TAP are suboptimal, suggesting a peptide-editing function for tapasin/TAP in addition to their role in enhancing peptide loading.

UR - http://www.scopus.com/inward/record.url?scp=0033083288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033083288&partnerID=8YFLogxK

M3 - Article

C2 - 9973410

AN - SCOPUS:0033083288

VL - 162

SP - 1530

EP - 1540

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 3

ER -