A point mutation in hla-a0201 results in failure to bind the tap complex and to present virus derived peptides to ctl

A. L. Peace-Brewer, L. Tussev, M. Matsui, G. Li, D. G. Ouinn, Jeffrey A Frelinger

Research output: Contribution to journalArticle

Abstract

We have investigated the interaction between TAP and MHC class I in presentation of viral antigen to cytotoxic T lymphocytes. Mutation of the HLA-A0201(A2.1) heavy chain from threonine to lysine at position 134 (T134K) results in a molecule which presents exogenous peptide but fails to efficiently present endogenously derived antigen. This defect in antigen presentation is also reflected in diminished cell surface expression and altered intracellular trafficking of T134K. The failure of T134K to present endogenous antigen can be overcome by delivery of peptide to the endoplasmic reticulum using a signal sequence, suggesting that the antigen presentation defect is restricted to TAP-dependent peptide loading. In permeabilized cells, the ability of T134K to load peptide in a TAPdependent manner is dramatically reduced compared to A2.1. Furthermore, by co-immunoprecipitation there is no detectable association of the T134K molecule with the TAP complex. These results show that mutation of threonine 134 of the heavy chain of A2.1 selectively affects TAP-association and peptide loading. Moreover, these studies suggest a requirement for the direct interaction of MHC class I heavy chain and TAP complex for efficient presentation of endogenous antigen.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996
Externally publishedYes

Fingerprint

trypsinogen activation peptide
Antigen Presentation
point mutation
Viruses
Point Mutation
peptides
Threonine
Antigens
viruses
Peptides
antigen presentation
Mutation
antigens
threonine
Viral Antigens
Cytotoxic T-Lymphocytes
Protein Sorting Signals
Immunoprecipitation
Endoplasmic Reticulum
Lysine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

A point mutation in hla-a0201 results in failure to bind the tap complex and to present virus derived peptides to ctl. / Peace-Brewer, A. L.; Tussev, L.; Matsui, M.; Li, G.; Ouinn, D. G.; Frelinger, Jeffrey A.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Peace-Brewer, A. L. ; Tussev, L. ; Matsui, M. ; Li, G. ; Ouinn, D. G. ; Frelinger, Jeffrey A. / A point mutation in hla-a0201 results in failure to bind the tap complex and to present virus derived peptides to ctl. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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AU - Ouinn, D. G.

AU - Frelinger, Jeffrey A

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