Physical and functional association of the major histocompatibility complex class I heavy chain alpha3 domain with the transporter associated with antigen processing.
Physical and functional association of the major histocompatibility complex class I heavy chain alpha3 domain with the transporter associated with antigen processing.
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主要组织相容性复合体 I 类重链 α3 结构域与抗原加工相关转运蛋白的物理和功能关联。
DOI：
10.1084/jem.187.6.865
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Vukmanović,S
中科院分区：
文献类型：
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作者：
Kulig,K;Nandi,D;Bacik,I;Monaco,JJ;Vukmanović,S
CD 8 +T淋巴细胞将抗原识别为通过细胞质蛋白加工而衍生的短的MHC I类相关肽。与抗原加工相关的转运蛋白将肽从细胞质转运到ER腔中，在那里它们与新生的I类分子结合。迄今为止，I-TAP类相互作用位点的确切位置仍不清楚。我们提供了该位点包含在重链α3结构域内的证据。用类似的MHC II类（H-2 IAd）β2结构域区域（aa 133-147）取代H-2Dbα3结构域的15个氨基酸部分（aa 219-233）导致表面表达丧失，在26°C存在过量肽和β2-微球蛋白的情况下孵育后可部分恢复。突变体H-2Db（Db219-233）与TAP复合物的结合较差，并且不能呈递需要TAP依赖性易位至ER的内源性来源的抗原肽。然而，这种呈递缺陷可以通过使用绕过TAP依赖性肽易位的ER靶向序列来克服。因此，α3结构域作为与TAP复合物相互作用（直接或间接）的重要位点，是TAP依赖性肽负载和I类表面表达所必需的。
CD8+T lymphocytes recognize antigens as short, MHC class I-associated peptides derived by processing of cytoplasmic proteins. The transporter associated with antigen processing translocates peptides from the cytosol into the ER lumen, where they bind to the nascent class I molecules. To date, the precise location of the class I-TAP interaction site remains unclear. We provide evidence that this site is contained within the heavy chain α3 domain. Substitution of a 15 amino acid portion of the H-2Dbα3 domain (aa 219-233) with the analogous MHC class II (H-2IAd) β2 domain region (aa 133-147) results in loss of surface expression which can be partially restored upon incubation at 26°C in the presence of excess peptide and β2-microglobulin. Mutant H-2Db(Db219-233) associates poorly with the TAP complex, and cannot present endogenously-derived antigenic peptides requiring TAP-dependent translocation to the ER. However, this presentation defect can be overcome through use of an ER targeting sequence which bypasses TAP-dependent peptide translocation. Thus, the α3 domain serves as an important site of interaction (directly or indirectly) with the TAP complex and is necessary for TAP-dependent peptide loading and class I surface expression.