He Xiao-lin, Radu Caius, Sidney John, Sette Alessandro, Ward E Sally, Garcia K Christopher
Department of Microbiology and Immunology, Stanford University School of Medicine, CA 94305, USA.
Immunity. 2002 Jul;17(1):83-94. doi: 10.1016/s1074-7613(02)00340-0.
Murine experimental allergic encephalomyelitis (EAE) is a useful model for the demyelinating, autoimmune disease multiple sclerosis. In the EAE system, the immunodominant N-terminal epitope of myelin basic protein (MBP) is an unusually short, weakly binding peptide antigen which elicits highly biased TCR chain usage. In the 2.2 A crystal structure of I-A(u)/MBP1-11 complex, only MBP residues 1-7 are bound toward one end of the peptide binding cleft. The fourth residue of MBP1-11 is located in an incompatible p6 pocket of I-A(u), thus explaining the short half-life of I-A(u) complexed with Ac1-11. MBP peptides extended at the C terminus of Ac1-11 result in dramatic affinity increases, likely attributed to register shifting to a higher affinity cryptic epitope, which could potentially mask the presentation of the immunodominant MBP1-11 peptide during thymic education.
小鼠实验性自身免疫性脑脊髓炎（EAE）是脱髓鞘自身免疫疾病多发性硬化的一种有用模型。在EAE系统中，髓鞘碱性蛋白（MBP）的免疫显性N端表位是一种异常短的、弱结合的肽抗原，它引发高度偏向的TCR链使用。在I-A(u)/MBP1-11复合物的2.2埃晶体结构中，只有MBP的1-7位残基朝向肽结合裂隙的一端结合。MBP1-11的第四个残基位于I-A(u)的不相容p6口袋中，因此解释了与Ac1-11复合的I-A(u)的短半衰期。在Ac1-11的C端延伸的MBP肽导致亲和力显著增加，这可能归因于向更高亲和力隐蔽表位的配准转移，这可能在胸腺教育期间潜在地掩盖免疫显性MBP1-11肽的呈递。
