Radu C G, Anderton S M, Firan M, Wraith D C, Ward E S
Center for Immunology and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75235-8576, USA.
Int Immunol. 2000 Nov;12(11):1553-60. doi: 10.1093/intimm/12.11.1553.
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.
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一个原型。在PL/J和B10.PL小鼠（H-2(u)单倍型）中，MBP的免疫显性表位由一个N端九聚体肽MBP1-9代表。迄今为止，尚未对MBP1-9特异性T细胞库进行定量分析。在本研究中，我们使用MHC II类四聚体证明，在用脊髓匀浆或MBP1-9免疫后，15000 - 70000个自身抗原特异性T(h)细胞在引流淋巴结中积聚。相比之下，在未免疫的H-2(u)小鼠中检测不到MBP1-9特异性T细胞，而在针对该表位的TCR转基因的未致敏小鼠中，MBP1-9特异性T细胞占CD4细胞的60%以上。结果表明，N端肽对I-A(u)的极低亲和力并不限制MBP1-9特异性T细胞扩展为大量的自身反应性T细胞池。因此，对MBP1-9的初次免疫反应在数量上与先前报道的CD4(+) T细胞对外源抗原的反应没有差异。
