A point mutation in HLA-A*0201 results in failure to bind the TAP complex and to present virus-derived peptides to CTL

Amy L. Peace-Brewer, Lynda G. Tussey, Masanori Matsui, Guoxuan Li, Daniel G. Quinn, Jeffrey A Frelinger

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

Mutating the HLA-A*0201 heavy chain from threonine to lysine at position 134 (T134K) results in a molecule that presents exogenous peptide, but cannot present endogenously derived antigen. This is reflected in diminished cell surface expression and altered intracellular trafficking of T134K. The failure of T134K to present endogenous antigen can be overcome by using an ER targeting sequence, suggesting that the antigen presentation defect is restricted to TAP-dependent peptide loading. The ability of T134K to load peptide in a TAP-dependent manner is dramatically reduced compared with HLA-A*0201. By coimmunoprecipitation there is no detectable association of the T134K molecule with the TAP complex. Thus, T134K selectively affects TAP association and peptide loading, suggesting a requirement for the direct interaction of MHC class I heavy chain and the TAP complex for efficient presentation of endogenous antigen.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalImmunity
Volume4
Issue number5
DOIs
StatePublished - May 1996
Externally publishedYes

Fingerprint

trypsinogen activation peptide
Antigen Presentation
Point Mutation
Viruses
Antigens
Peptides
Threonine
Lysine
HLA-A*02:01 antigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

A point mutation in HLA-A*0201 results in failure to bind the TAP complex and to present virus-derived peptides to CTL. / Peace-Brewer, Amy L.; Tussey, Lynda G.; Matsui, Masanori; Li, Guoxuan; Quinn, Daniel G.; Frelinger, Jeffrey A.

In: Immunity, Vol. 4, No. 5, 05.1996, p. 505-514.

Research output: Contribution to journalArticle

Peace-Brewer, Amy L. ; Tussey, Lynda G. ; Matsui, Masanori ; Li, Guoxuan ; Quinn, Daniel G. ; Frelinger, Jeffrey A. / A point mutation in HLA-A*0201 results in failure to bind the TAP complex and to present virus-derived peptides to CTL. In: Immunity. 1996 ; Vol. 4, No. 5. pp. 505-514.
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