Jansson L, Diener P, Engström A, Olsson T, Holmdahl R
Department of Medical Inflammation Research, Lund University, Sweden.
Eur J Immunol. 1995 Aug;25(8):2195-200. doi: 10.1002/eji.1830250812.
B10.RIII mice develop chronic and relapsing experimental autoimmune encephalomyelitis (EAE) after immunization with the myelin basic protein (MBP) peptide 89-101 (VHFFKNIVTPRTP). To investigate the basis for the chronicity of the disease, the subsequent development of an immune responses to other parts of the MBP protein were investigated. Onset of disease occurs 9-25 days after immunization with MBP89-101. T cell responses towards a series of MBP peptides were assessed in an enzyme-linked immunospot assay detecting single cells secreting IFN-gamma. There were responses not only to MBP89-101, but also towards peptides derived from sequences outside of MBP89-101. These peptides were of two kinds: those with sequences completely outside the 89-101 stretch of MBP; and those sharing a short sequence with MBP89-101 depending on alternative splicing of MBP mRNA. Immunization with these peptides also produced chronic EAE and a spreading of the immune response to other MBP peptides. Immunization with stepped peptides around the relevant region (MBP87-110) showed that peptides sharing a 6-amino-acid motif induced EAE after immunization. After MBP89-101 peptide immunization, T cells isolated from lymph nodes did not cross-react in vitro to the other peptides sharing this motif. We suggest that one mechanism for the development of relapses during the disease course is the recruitment of new T cells with specificity for MBP peptides not derived from the peptide used for immunization. This is the first time such a mechanism has been demonstrated in a chronic autoimmune disease model.
用髓鞘碱性蛋白（MBP）肽89 - 101（VHFFKNIVTPRTP）免疫后，B10.RIII小鼠会发生慢性复发性实验性自身免疫性脑脊髓炎（EAE）。为了研究该疾病慢性化的基础，我们研究了对MBP蛋白其他部分的免疫反应的后续发展。用MBP89 - 101免疫后9 - 25天疾病发作。在检测分泌γ干扰素的单细胞的酶联免疫斑点试验中评估了对一系列MBP肽的T细胞反应。不仅对MBP89 - 101有反应，而且对源自MBP89 - 101序列之外的肽也有反应。这些肽有两种：那些序列完全在MBP的89 - 101片段之外的；以及那些根据MBP mRNA的可变剪接与MBP89 - 101共享短序列的。用这些肽免疫也产生了慢性EAE，并使免疫反应扩散到其他MBP肽。用相关区域（MBP87 - 110）周围的阶梯肽免疫表明，共享6个氨基酸基序的肽免疫后会诱发EAE。用MBP89 - 101肽免疫后，从淋巴结分离的T细胞在体外不会与共享该基序的其他肽发生交叉反应。我们认为，疾病过程中复发发展的一种机制是招募对并非源自用于免疫的肽的MBP肽具有特异性的新T细胞。这是首次在慢性自身免疫性疾病模型中证明这种机制。
