Hinz Andreas, Jedamzick Johanna, Herbring Valentina, Fischbach Hanna, Hartmann Jessica, Parcej David, Koch Joachim, Tampé Robert
From the Institute of Biochemistry, Biocenter and.
Georg-Speyer-Haus, Institute for Tumor Biology and Experimental Therapy, Paul-Ehrlich-Str. 42, 60596 Frankfurt/M., Germany.
J Biol Chem. 2014 Nov 28;289(48):33109-17. doi: 10.1074/jbc.M114.609263. Epub 2014 Oct 15.
Antigen presentation to cytotoxic T lymphocytes via major histocompatibility complex class I (MHC I) molecules depends on the heterodimeric transporter associated with antigen processing (TAP). For efficient antigen supply to MHC I molecules in the ER, TAP assembles a macromolecular peptide-loading complex (PLC) by recruiting tapasin. In evolution, TAP appeared together with effector cells of adaptive immunity at the transition from jawless to jawed vertebrates and diversified further within the jawed vertebrates. Here, we compared TAP function and interaction with tapasin of a range of species within two classes of jawed vertebrates. We found that avian and mammalian TAP1 and TAP2 form heterodimeric complexes across taxa. Moreover, the extra N-terminal domain TMD0 of mammalian TAP1 and TAP2 as well as avian TAP2 recruits tapasin. Strikingly, however, only TAP1 and TAP2 from the same taxon can form a functional heterodimeric translocation complex. These data demonstrate that the dimerization interface between TAP1 and TAP2 and the tapasin docking sites for PLC assembly are conserved in evolution, whereas elements of antigen translocation diverged later in evolution and are thus taxon specific.
通过主要组织相容性复合体I类（MHC I）分子向细胞毒性T淋巴细胞呈递抗原依赖于与抗原加工相关的异二聚体转运体（TAP）。为了将抗原有效地供应到内质网中的MHC I分子，TAP通过招募塔帕辛组装一个大分子肽装载复合体（PLC）。在进化过程中，TAP与适应性免疫的效应细胞一起出现在从无颌脊椎动物到有颌脊椎动物的过渡阶段，并在有颌脊椎动物中进一步分化。在这里，我们比较了两类有颌脊椎动物中一系列物种的TAP功能以及与塔帕辛的相互作用。我们发现，鸟类和哺乳动物的TAP1和TAP2跨分类群形成异二聚体复合物。此外，哺乳动物TAP1和TAP2以及鸟类TAP2的额外N端结构域TMD0招募塔帕辛。然而，引人注目的是，只有来自同一分类群的TAP1和TAP2才能形成功能性的异二聚体转运复合物。这些数据表明，TAP1和TAP2之间的二聚化界面以及用于PLC组装的塔帕辛对接位点在进化中是保守的，而抗原转运元件在进化后期发生了分化，因此是分类群特异性的。
