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

AL PeaceBrewer, LG Tussey, M Matsui, GX Li, Daniel Quinn, JA Frelinger

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    124 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
    Pages (from-to)505-514
    JournalImmunity
    Volume4
    Issue number5
    DOIs
    Publication statusPublished - May 1996

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