Momburg F, Roelse J, Howard J C, Butcher G W, Hämmerling G J, Neefjes J J
Tumor Immunology Program, German Cancer Research Centre, Heidelberg.
Nature. 1994 Feb 17;367(6464):648-51. doi: 10.1038/367648a0.
Major histocompatibility complex (MHC) class I molecules present peptides from degraded intracellular antigens to CD8+ T cells. These peptides are translocated in an ATP-dependent fashion into the lumen of the endoplasmic reticulum (ER) for binding to class I molecules by means of the MHC-encoded transporters associated with antigen processing, TAP1 and TAP2. These are members of a family of proteins containing an ATP-binding cassette and form heterodimers in the ER membrane. Defects in the genes encoding TAP1 or TAP2 account for impaired class I assembly and antigen presentation in several human and rodent cell lines. Whereas MHC class I molecules select peptides according to binding motifs, it is not clear to what extent the TAP1-TAP2 transporters have peptide sequence and length specificity. Previous studies of the rat MHC class I molecule RT1Aa, suggested a specific conveyance of peptides by rat TAP1-TAP2. Here we substitute the amino- and carboxy-terminal and the penultimate amino-acid residues of model peptides to show that these residues influence the efficiency of transport. Human TAP and rat TAPa translocated peptides with hydrophobic and basic C termini, whereas mouse TAP and rat TAPu preferred peptides with hydrophobic C termini. This pattern correlates with the predominant peptide binding profiles of mouse and human class I molecules.
主要组织相容性复合体（MHC）I类分子将降解的细胞内抗原产生的肽段呈递给CD8 + T细胞。这些肽段以ATP依赖的方式转运到内质网（ER）腔中，通过与抗原加工相关的MHC编码转运体TAP1和TAP2与I类分子结合。它们是含有ATP结合盒的蛋白质家族成员，在ER膜中形成异二聚体。编码TAP1或TAP2的基因缺陷导致几种人类和啮齿动物细胞系中I类组装和抗原呈递受损。虽然MHC I类分子根据结合基序选择肽段，但尚不清楚TAP1 - TAP2转运体在多大程度上具有肽段序列和长度特异性。先前对大鼠MHC I类分子RT1Aa的研究表明大鼠TAP1 - TAP2对肽段有特异性转运作用。在这里，我们替换了模型肽段的氨基末端、羧基末端和倒数第二个氨基酸残基，以表明这些残基会影响转运效率。人TAP和大鼠TAPa转运具有疏水和碱性C末端的肽段，而小鼠TAP和大鼠TAPu则更喜欢具有疏水C末端的肽段。这种模式与小鼠和人类I类分子的主要肽段结合谱相关。
