A point mutation in HLA-A*0201 results in failure to bind the TAP complex and to present virus-derived peptides to CTL.
A point mutation in HLA-A*0201 results in failure to bind the TAP complex and to present virus-derived peptides to CTL.
复制标题
DOI：
10.1016/s1074-7613(00)80416-1
复制
发表时间：
1996-05
期刊：
影响因子：
32.4
通讯作者：
A. Peace-Brewer;Lynda Tussey;Masanori Matsui;Guoxuan Li;D. Quinn;J. A. Frelinger
中科院分区：
文献类型：
--
作者：
A. Peace-Brewer;Lynda Tussey;Masanori Matsui;Guoxuan Li;D. Quinn;J. A. Frelinger
HLAA0201重链134位(T134K)由苏氨酸突变为赖氨酸，导致分子呈现外源性多肽，但不呈现内源性抗原。这反映在T134K的细胞表面表达减少和细胞内运输改变上。T134K不能提呈内源性抗原可以通过使用ER靶向序列来克服，这表明抗原提呈缺陷仅限于TAP依赖的多肽负载。与HLA-A*0201相比，T134K以TAP依赖的方式载入肽的能力显著降低。通过免疫共沉淀，没有检测到T134K分子与TAP复合体的结合。因此，T134K选择性地影响TAP结合和多肽负载，这表明需要MHC I类重链和TAP复合体的直接相互作用才能有效地递呈内源性抗原。
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.