Neisig A, Wubbolts R, Zang X, Melief C, Neefjes J
Department of Cellular Biochemistry, The Netherlands Cancer Institute, Amsterdam.
J Immunol. 1996 May 1;156(9):3196-206.
MHC class I molecules bind peptides that are translocated from the cytosol into the endoplasmic reticulum by the peptide transporter associated with antigen processing (TAP). Class I heterodimers have been shown to associate with TAP and are released when loaded with peptide. Here, we show the existence of two pools of class I heterodimers, one associated with TAP and one that is free. Whereas the free pool is recognized by the class I-specific Ab W6/32, the TAP-associated pool is not. Analysis of several class I alleles shows binding to TAP with different efficiencies, even at the earliest time points of MHC class I assembly. Most HLA-A and -C alleles tested interacted efficiently with TAP, whereas a considerable number of HLA-B alleles associated very inefficiently or not at all with TAP. This was also observed in cells with nonfunctional TAP. Sequence comparison of the different class I alleles allowed the definition of amino acids in the peptide binding groove that might be involved in TAP association. Binding of peptides to two different pools of class I heterodimers may ensure efficient peptide association in an environment where peptides have a short life span.
MHC I类分子结合通过与抗原加工相关的肽转运体（TAP）从胞质溶胶转运至内质网的肽段。已证实I类异二聚体与TAP结合，并在装载肽段后释放。在此，我们展示了存在两类I类异二聚体，一类与TAP结合，另一类是游离的。游离的I类异二聚体可被I类特异性抗体W6/32识别，而与TAP结合的那一类则不能。对多个I类等位基因的分析表明，即使在MHC I类组装的最早时间点，它们与TAP的结合效率也有所不同。大多数检测的HLA - A和 - C等位基因与TAP高效相互作用，而相当数量的HLA - B等位基因与TAP的结合效率非常低或根本不结合。在TAP功能缺失的细胞中也观察到了这种情况。对不同I类等位基因的序列比较确定了肽结合槽中可能参与与TAP结合的氨基酸。肽段与两类不同的I类异二聚体结合可能确保在肽段寿命较短的环境中肽段的有效结合。
