EVOLUTIONARY CONSERVATION OF MAJOR HISTOCOMPATIBILITY COMPLEX-DR/PEPTIDE/T-CELL INTERACTIONS IN PRIMATES
EVOLUTIONARY CONSERVATION OF MAJOR HISTOCOMPATIBILITY COMPLEX-DR/PEPTIDE/T-CELL INTERACTIONS IN PRIMATES
复制标题
DOI：
10.1084/jem.177.4.979
复制
发表时间：
1993-04-01
影响因子：
15.3
通讯作者：
BONTROP, RE
中科院分区：
文献类型：
--
作者：
GELUK, A;ELFERINK, DG;BONTROP, RE
许多主要组织相容性复合体（MHC）多态性起源于物种形成之前的古老结构。因此，Mhc-DRB 1 *03等位基因谱系的成员不仅存在于人类中，而且也存在于黑猩猩和恒河猴中。这强调了Mhc-DRB 1 *03成员必须存在于这些灵长类物种的共同祖先中，这些灵长类物种生活在大约3000万年前。然而，由于遗传变异的积累，Mhc-DRB 1 *03谱系的等位基因表现出物种独特的序列。为了研究这种保守和变异的生物学重要性，我们研究了各种跨物种Mhc-DRB 1 *03谱系成员的结合和抗原呈递能力。本研究表明，麻风分枝杆菌和M.结核病不仅与HLA-DR 17结合（3），而且与一些黑猩猩和恒河猴II类阳性细胞结合。相应的人类，黑猩猩，和恒河猴Mhc-DRB 1 *03谱系成员的比较揭示了独特的共享的氨基酸残基的存在下，在位置9-13和26-31，抗原结合位点的p3-13结合的关键。此外，它表明，结合p3-13的几种非人灵长类动物抗原呈递细胞可以激活HLA-DR 17限制性T细胞。然而，Mhc-DRB 1 *03谱系成员中的某些氨基酸替换并不影响肽结合或T细胞识别。因此，这些研究表明，MHC II类分子的抗原结合位点内的一些多态性氨基酸残基（基序）对于肽结合和T细胞受体的识别至关重要，已经保守了超过3000万年。
Many major histocompatibility complex (MHC) polymorphisms originate from ancient structures that predate speciation. As a consequence, members of the Mhc-DRB1*03 allelic lineage are not only present in humans but in chimpanzees and rhesus macaques as well. This emphasizes that Mhc-DRB1*03 members must have been present in a common ancestor of these primate species that lived about 30 million years ago. Due to the accumulation of genetic variation, however, alleles of the Mhc-DRB1*03 lineage exhibit species-unique sequences. To investigate the biological importance of such conservation and variation, we have studied both the binding and antigen presentation capacity of various trans-species Mhc-DRB1*03 lineage members. Here we show that p3-13 of the 65-kD heat-shock protein (hsp65) of Mycobacterium leprae and M. tuberculosis binds not only to HLA-DR17(3) but also to some chimpanzee and rhesus macaque class II-positive cells. Comparison of the corresponding human, chimpanzee, and rhesus macaque Mhc-DRB1*03 lineage members revealed the presence of uniquely shared amino acid residues, at positions 9-13 and 26-31, of the antigen-binding site that are critical for p3-13 binding. In addition it is shown that several nonhuman primate antigen-presenting cells that bind p3-13 can activate HLA-DR17-restricted T cells. Certain amino acid replacements, however, in Mhc-DRB1*03 lineage members did not influence peptide binding or T cell recognition. Therefore, these studies demonstrate that some polymorphic amino acid residues (motifs) within the antigen-binding site of MHC class II molecules that are crucial for peptide binding and recognition by the T cell receptor have been conserved for over 30 million years.