McRae B L, Karandikar N J, Miller S D
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
J Neuroimmunol. 1997 May;75(1-2):156-62. doi: 10.1016/s0165-5728(97)00014-3.
Peptide-specific tolerance with PLP139-151 peptide analogs was used to compare the fine antigen-specificity requirements at both the inductive and effector phases of relapsing EAE (R-EAE). A PLP139-151 analog peptide containing a single substitution at the primary T cell receptor (TcR) contact residue (A144) did not induce proliferation in PLP139-151-primed CD4+ T cells. In addition, tolerance induced with ECDI-treated. A144-coupled splenocytes failed to prevent the inductive phase of PLP139-151-induced R-EAE or to inhibit the induction of peptide-specific DTH indicating that naive PLP139-151-specific T cells do not react with the A144 peptide analog. In contrast, A144-coupled splenocytes did prevent the expression of the effector phase of R-EAE and inhibited the elicitation of peptide-specific DTH responses upon administration to mice seven days after immunization with PLP139-151. The results provide in vivo evidence that "antigen-experienced' T cells recognize a broader repertoire of antigens than do naive T cells and have important implications for the regulation of immune responses and for advancing our understanding of the pathogenesis and treatment of autoimmune disease.
使用PLP139 - 151肽类似物诱导的肽特异性耐受来比较复发性实验性自身免疫性脑脊髓炎（R - EAE）诱导期和效应期的精细抗原特异性需求。一种在主要T细胞受体（TcR）接触残基（A144）处有单个取代的PLP139 - 151类似物肽，不能诱导经PLP139 - 151致敏的CD4 + T细胞增殖。此外，用ECDI处理的A144偶联脾细胞诱导的耐受未能阻止PLP139 - 151诱导的R - EAE的诱导期，也不能抑制肽特异性迟发型超敏反应（DTH）的诱导，这表明未致敏的PLP139 - 151特异性T细胞不与A144肽类似物发生反应。相反，A144偶联脾细胞确实阻止了R - EAE效应期的表达，并在给小鼠注射PLP139 - 151免疫七天后给药时，抑制了肽特异性DTH反应的激发。这些结果提供了体内证据，即“抗原致敏的”T细胞比未致敏的T细胞识别更广泛的抗原库，这对免疫反应的调节以及推进我们对自身免疫性疾病发病机制和治疗的理解具有重要意义。
