Virus subversion of the MHC class I peptide-loading complex

Immunity. 2003 Jan;18(1):121-30. doi: 10.1016/s1074-7613(02)00509-5.

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 gamma(2)-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Antigen Presentation
  • Antiporters / deficiency
  • Antiporters / genetics
  • Antiporters / metabolism
  • Calreticulin / metabolism
  • Cell Line
  • Down-Regulation
  • Gammaherpesvirinae / immunology*
  • Gammaherpesvirinae / metabolism*
  • Gammaherpesvirinae / pathogenicity
  • Gene Targeting
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Immunoglobulins / deficiency
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • Membrane Transport Proteins
  • Mice
  • Mutation
  • Viral Proteins / immunology*
  • Viral Proteins / metabolism*
  • beta 2-Microglobulin / deficiency
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • Antiporters
  • Calreticulin
  • Histocompatibility Antigens Class I
  • Immunoglobulins
  • Membrane Transport Proteins
  • TAP1 protein, human
  • Tap1 protein, mouse
  • Tap2 protein, mouse
  • Viral Proteins
  • beta 2-Microglobulin
  • tapasin
  • TAP2 protein, human