SELECTIVITY OF MHC-ENCODED PEPTIDE TRANSPORTERS FROM HUMAN, MOUSE AND RAT
SELECTIVITY OF MHC-ENCODED PEPTIDE TRANSPORTERS FROM HUMAN, MOUSE AND RAT
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DOI：
10.1038/367648a0
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发表时间：
1994-02-17
期刊：
影响因子：
64.8
通讯作者：
NEEFJES, JJ
中科院分区：
文献类型：
--
作者：
MOMBURG, F;ROELSE, J;NEEFJES, JJ
主要的组织相容性复合体（MHC）I类分子将降解的细胞内抗原的肽呈递给CD 8（+）T细胞（1）。这些肽以ATP依赖性方式（2-4）易位到内质网（ER）的内腔中，以通过与抗原加工相关的MHC编码的转运蛋白TAP 1和TAP 2结合I类分子（5，6）。这些是含有ATP结合盒的蛋白质家族的成员，并在ER膜中形成异二聚体（7-10）。编码TAP 1或TAP 2的基因的缺陷导致在几种人和啮齿动物细胞系中I类组装和抗原呈递受损（7，11 -13）。尽管MHC I类分子根据结合基序选择肽（14-17），但TAP 1-TAP 2转运蛋白在何种程度上具有肽序列和长度特异性尚不清楚。先前对大鼠MHC I类分子RT 1A（a）的研究表明，大鼠TAP 1-TAP 2可特异性转运肽（参考文献18）。在这里，我们取代的氨基和羧基末端和倒数第二个氨基酸残基的模型肽，以表明这些残基影响的运输效率。人TAP和大鼠TAP（a）具有疏水性和碱性C末端的易位肽，而小鼠TAP和大鼠TAP（u）优选具有疏水性C末端的肽。这种模式与小鼠和人I类分子的主要肽结合谱相关。
MAJOR histocompatibility complex (MHC) class I molecules present peptides from degraded intracellular antigens to CD8(+) T cells(1). These peptides are translocated in an ATP-dependent fashion(2-4) into the lumen of the endoplasmic reticulum (ER) for binding to class I molecules(5,6) 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(7-10). Defects in the genes encoding TAP1 or TAP2 account for impaired class I assembly and antigen presentation in several human and rodent cell lines(7,11-13). Whereas MHC class I molecules select peptides according to binding motifs(14-17), 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, RT1A(a), suggested a specific conveyance of peptides by rat TAP1-TAP2 (ref. 18). 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 TAP(a) translocated peptides with hydrophobic and basic C termini, whereas mouse TAP and rat TAP(u) preferred peptides with hydrophobic C termini. This pattern correlates with the predominant peptide binding profiles of mouse and human class I molecules.