Detection of autoreactive T cells in H-2u mice using peptide-MHC multimers.
Detection of autoreactive T cells in H-2u mice using peptide-MHC multimers.
复制标题
DOI：
10.1093/intimm/12.11.1553
复制
发表时间：
2000-11
影响因子：
4.4
通讯作者：
C. Radu;S. Anderton;Mihail Firan;D. Wraith;E. Ward
中科院分区：
文献类型：
--
作者：
C. Radu;S. Anderton;Mihail Firan;D. Wraith;E. Ward
髓鞘碱性蛋白（MBP）特异性T细胞在实验性自身免疫性脑脊髓炎（EAE）的发病机制中起关键作用，EAE是T细胞介导的自身免疫的原型。在PL/J和B10.PL小鼠（H-2（u）单倍型）中，MBP的免疫显性表位由N-末端九聚体肽MBP 1 -9代表。迄今为止，尚未定量分析MBP 1 -9特异性T细胞库。在本研究中，我们证明，使用MHC II类四聚体，15，000 - 70，000自身抗原特异性T（h）细胞在脊髓匀浆或MBP 1 -9免疫后在引流淋巴结中积累。相比之下，在未免疫的H-2（u）小鼠中无法检测到MBP 1 -9特异性T细胞，并且在对该表位特异性TCR转基因的幼稚小鼠中占CD 4细胞的>60%。结果表明，N-末端肽对I-A（u）的极低亲和力不会限制MBP 1 -9特异性T细胞扩增成相当大的自身反应性T细胞库。因此，对MBP 1 -9的初次免疫应答与先前报道的对外源抗原的CD 4（+）T细胞应答在数量上没有差异。
Myelin basic protein (MBP)-specific T cells play a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity. In PL/J and B10.PL mice (H-2(u) haplotype), the immunodominant epitope of MBP is represented by an N-terminal nonameric peptide, MBP1-9. To date, the MBP1-9-specific T cell repertoire has not been analyzed in quantitative terms. In the present study we demonstrate, using MHC class II tetramers, that 15,000-70,000 self-antigen-specific T(h) cells accumulate in the draining lymph nodes following immunization with spinal cord homogenate or MBP1-9. In contrast, MBP1-9-specific T cells are undetectable in unimmunized H-2(u) mice and represent >60% of the CD4 cells in naive mice transgenic for a TCR specific for this epitope. The results suggest that the extremely low affinity of the N-terminal peptide for I-A(u) does not limit the MBP1-9-specific T cells from expanding into a sizeable pool of autoreactive T cells. Therefore, the primary immune response to MBP1-9 does not differ quantitatively from previously reported CD4(+) T cell responses to foreign antigens.