Gaur A, Boehme S A, Chalmers D, Crowe P D, Pahuja A, Ling N, Brocke S, Steinman L, Conlon P J
Neurocrine Biosciences, San Diego, CA 92121, USA.
J Neuroimmunol. 1997 Apr;74(1-2):149-58. doi: 10.1016/s0165-5728(96)00220-2.
T-cells specific for a region of human myelin basic protein, amino acids 87-99 (hMBP87-99), have been implicated in the development of multiple sclerosis (MS) a demyelinating disease of the central nervous system. Administration of soluble altered peptide ligand (APL), made by substituting native residues with alanine at either positions 91(91K > A or A91) or 97 (97R > A or A97) in the hMBP87-99 peptide, blocked the development of chronic relapsing experimental autoimmune encephalomyelitis (R-EAE), in the SJL mouse. The non-encephalitogenic APL A91, appears to induce cytokine shifts from Th1 to Th2 in the target T-cells, whereas the encephalitogenic superagonist APL A97 causes deletion of the MBP87-99 responsive cells. Thus, single amino acid changes at different positions in the same peptide epitope can lead to APL capable of controlling auto-immune disease by different mechanisms.
对人髓鞘碱性蛋白87 - 99位氨基酸区域（hMBP87 - 99）具有特异性的T细胞与多发性硬化症（MS）——一种中枢神经系统脱髓鞘疾病的发病机制有关。给予可溶性改变肽配体（APL），其通过将hMBP87 - 99肽中91位（91K > A或A91）或97位（97R > A或A97）的天然残基用丙氨酸替代而制成，可阻断SJL小鼠慢性复发性实验性自身免疫性脑脊髓炎（R - EAE）的发展。无致脑炎性的APL A91似乎能诱导靶T细胞中的细胞因子从Th1向Th2转变，而具有致脑炎性的超级激动剂APL A97则导致MBP87 - 99反应性细胞的缺失。因此，同一肽表位不同位置的单个氨基酸变化可导致能够通过不同机制控制自身免疫性疾病的APL。
