Virus subversion of the MHC class I peptide-loading complex

Lonnie Lybarger, Xiaoli Wang, Michael R. Harris, Herbert W. Virgin IV, Ted H. Hansen

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Many viral proteins modulate class I expression, yet, in general, their mechanisms of specific class I recognition are poorly understood. The mK3 protein of γ2-Herpesvirus 68 targets the degradation of nascent class I molecules via the ubiquitin/proteasome pathway. Here, we identify cellular components of the MHC class I assembly machinery, TAP and tapasin, that are required for mK3 function. mK3 failed to regulate class I in TAP- or tapasin-deficient cells, and mK3 interacted with TAP/tapasin, even in the absence of class I. Expression of mK3 resulted in the ubiquitination of TAP/tapasin-associated class I, and mutants of class I incapable of TAP/tapasin interaction were unaffected by mK3. Thus, mK3 subverts TAP/tapasin to specifically target class I molecules for destruction.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
JournalImmunity
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Viruses
Peptides
Herpesviridae
Ubiquitination
Viral Proteins
Proteasome Endopeptidase Complex
Ubiquitin
tapasin
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Lybarger, L., Wang, X., Harris, M. R., Virgin IV, H. W., & Hansen, T. H. (2003). Virus subversion of the MHC class I peptide-loading complex. Immunity, 18(1), 121-130. https://doi.org/10.1016/S1074-7613(02)00509-5

Virus subversion of the MHC class I peptide-loading complex. / Lybarger, Lonnie; Wang, Xiaoli; Harris, Michael R.; Virgin IV, Herbert W.; Hansen, Ted H.

In: Immunity, Vol. 18, No. 1, 01.01.2003, p. 121-130.

Research output: Contribution to journalArticle

Lybarger, L, Wang, X, Harris, MR, Virgin IV, HW & Hansen, TH 2003, 'Virus subversion of the MHC class I peptide-loading complex', Immunity, vol. 18, no. 1, pp. 121-130. https://doi.org/10.1016/S1074-7613(02)00509-5
Lybarger, Lonnie ; Wang, Xiaoli ; Harris, Michael R. ; Virgin IV, Herbert W. ; Hansen, Ted H. / Virus subversion of the MHC class I peptide-loading complex. In: Immunity. 2003 ; Vol. 18, No. 1. pp. 121-130.
@article{38d3fd51a73d41faa7c3093dd75ed211,
title = "Virus subversion of the MHC class I peptide-loading complex",
abstract = "Many viral proteins modulate class I expression, yet, in general, their mechanisms of specific class I recognition are poorly understood. The mK3 protein of γ2-Herpesvirus 68 targets the degradation of nascent class I molecules via the ubiquitin/proteasome pathway. Here, we identify cellular components of the MHC class I assembly machinery, TAP and tapasin, that are required for mK3 function. mK3 failed to regulate class I in TAP- or tapasin-deficient cells, and mK3 interacted with TAP/tapasin, even in the absence of class I. Expression of mK3 resulted in the ubiquitination of TAP/tapasin-associated class I, and mutants of class I incapable of TAP/tapasin interaction were unaffected by mK3. Thus, mK3 subverts TAP/tapasin to specifically target class I molecules for destruction.",
author = "Lonnie Lybarger and Xiaoli Wang and Harris, {Michael R.} and {Virgin IV}, {Herbert W.} and Hansen, {Ted H.}",
year = "2003",
month = "1",
day = "1",
doi = "10.1016/S1074-7613(02)00509-5",
language = "English (US)",
volume = "18",
pages = "121--130",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Virus subversion of the MHC class I peptide-loading complex

AU - Lybarger, Lonnie

AU - Wang, Xiaoli

AU - Harris, Michael R.

AU - Virgin IV, Herbert W.

AU - Hansen, Ted H.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Many viral proteins modulate class I expression, yet, in general, their mechanisms of specific class I recognition are poorly understood. The mK3 protein of γ2-Herpesvirus 68 targets the degradation of nascent class I molecules via the ubiquitin/proteasome pathway. Here, we identify cellular components of the MHC class I assembly machinery, TAP and tapasin, that are required for mK3 function. mK3 failed to regulate class I in TAP- or tapasin-deficient cells, and mK3 interacted with TAP/tapasin, even in the absence of class I. Expression of mK3 resulted in the ubiquitination of TAP/tapasin-associated class I, and mutants of class I incapable of TAP/tapasin interaction were unaffected by mK3. Thus, mK3 subverts TAP/tapasin to specifically target class I molecules for destruction.

AB - Many viral proteins modulate class I expression, yet, in general, their mechanisms of specific class I recognition are poorly understood. The mK3 protein of γ2-Herpesvirus 68 targets the degradation of nascent class I molecules via the ubiquitin/proteasome pathway. Here, we identify cellular components of the MHC class I assembly machinery, TAP and tapasin, that are required for mK3 function. mK3 failed to regulate class I in TAP- or tapasin-deficient cells, and mK3 interacted with TAP/tapasin, even in the absence of class I. Expression of mK3 resulted in the ubiquitination of TAP/tapasin-associated class I, and mutants of class I incapable of TAP/tapasin interaction were unaffected by mK3. Thus, mK3 subverts TAP/tapasin to specifically target class I molecules for destruction.

UR - http://www.scopus.com/inward/record.url?scp=0037237794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037237794&partnerID=8YFLogxK

U2 - 10.1016/S1074-7613(02)00509-5

DO - 10.1016/S1074-7613(02)00509-5

M3 - Article

C2 - 12530981

AN - SCOPUS:0037237794

VL - 18

SP - 121

EP - 130

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 1

ER -