Das M R, Cohen A, Zamvil S S, Offner H, Kuchroo V K
Department of Neurology, Harvard Medical School, Boston, MA, USA.
J Neuroimmunol. 1996 Dec;71(1-2):3-10. doi: 10.1016/s0165-5728(96)00107-5.
Experimental allergic encephalomyelitis (EAE) is inducible in experimental animals immunized with myelin basic protein (MBP), proteolipid protein (PLP) or their peptides. We compared T-cell responses to encephalitogenic epitopes of PLP(43-64) and MBP(Ac1-11) in a single mouse strain, (PL/J x SJL)F1. MBP(1-11)-specific T-cell hybridomas expressed predominantly TCR V beta 8 or V beta 4, while PLP(43-64)-specific hybridomas expressed a diverse TCR repertoire. To analyze the biologic significance of the TCR repertoire (limited vs. diverse) to disease susceptibility, we pretreated mice with a superantigen (SEB), and then induced disease with these autoantigens. Mice injected with SEB and immunized with MBP(Ac1-11) showed significant inhibition of EAE, whereas SEB-pretreated mice immunized with PLP(43-64) had an increased severity of EAE and developed a chronic disease. These data demonstrate that prior exposure to microbial superantigens can significantly alter the autoimmune disease course depending upon the TCR repertoire used by the autoantigen.
实验性变应性脑脊髓炎（EAE）可在经髓鞘碱性蛋白（MBP）、蛋白脂蛋白（PLP）或其肽免疫的实验动物中诱导产生。我们比较了单一小鼠品系（PL/J×SJL）F1中T细胞对PLP(43 - 64)和MBP(Ac1 - 11)致脑炎表位的反应。MBP(1 - 11)特异性T细胞杂交瘤主要表达TCR Vβ8或Vβ4，而PLP(43 - 64)特异性杂交瘤表达多种TCR库。为分析TCR库（有限型与多样型）对疾病易感性的生物学意义，我们用超抗原（SEB）预处理小鼠，然后用这些自身抗原诱导疾病。注射SEB并用MBP(Ac1 - 11)免疫的小鼠EAE明显受到抑制，而用PLP(43 - 64)免疫的SEB预处理小鼠EAE严重程度增加并发展为慢性疾病。这些数据表明，预先接触微生物超抗原可根据自身抗原所使用的TCR库显著改变自身免疫疾病进程。
