Stepaniak J A, Gould K E, Sun D, Swanborg R H
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Immunol. 1995 Sep 1;155(5):2762-9.
We compared the T cell responses of Lewis (LEW) and DA rats to guinea pig myelin basic protein (MBP), the synthetic peptides corresponding to the epitopes that are encephalitogenic in the LEW strain (MBP73-86, MBP68-86, and MBP87-99), and bovine proteolipid protein (PLP). DA and LEW rats were susceptible to experimental autoimmune encephalomyelitis (EAE) induced with MBP or MBP68-86, but the peptide was less active in DA rats than in intact MBP molecule. MBP73-86 and MBP87-99 induced EAE in LEW rats but not in the DA strain. MBP89-169 was also encephalitogenic in DA rats. Encephalitogenic CDa+ T cell lines and clones derived from MBP-sensitized DA rats secreted IFN-gamma and TNF-alpha and proliferated to MBP and MBP89-169, but not to MBP68-88. However, T cells from MBP68-86-sensitized DA or LEW rats proliferated specifically in an I-A-restricted response to MBP68-86. T cells from MBP87-99-immunized LEW rats responded to MBP87-99 in the context of I-E, whereas the peptide-specific response of MBP87-99 immunized DA rats was I-A-restricted, although FACScan analysis indicated that DA rats express both I-A and I-E. DA rats were also highly susceptible to EAE induced with PLP; 0.6 nmol was Encephalitogenic for DA rats, but did not induce clinical EAE in LEW rats. Although both DA and LEW rats are highly susceptible to EAE, we demonstrate marked differences in the array of myelin epitopes capable of inducing the disease, as well as the MHC restriction of these epitopes, between the two rat strains.
我们比较了Lewis（LEW）大鼠和DA大鼠对豚鼠髓鞘碱性蛋白（MBP）、与LEW品系中具有致脑炎性的表位相对应的合成肽（MBP73 - 86、MBP68 - 86和MBP87 - 99）以及牛蛋白脂蛋白（PLP）的T细胞反应。DA大鼠和LEW大鼠对用MBP或MBP68 - 86诱导的实验性自身免疫性脑脊髓炎（EAE）敏感，但该肽在DA大鼠中的活性低于完整的MBP分子。MBP73 - 86和MBP87 - 99在LEW大鼠中诱导EAE，但在DA品系中不诱导。MBP89 - 169在DA大鼠中也具有致脑炎性。源自MBP致敏的DA大鼠的致脑炎性CD4⁺T细胞系和克隆分泌γ干扰素和肿瘤坏死因子-α，并对MBP和MBP89 - 169增殖，但对MBP68 - 88不增殖。然而，来自MBP68 - 86致敏的DA或LEW大鼠的T细胞在对MBP68 - 86的I - A限制反应中特异性增殖。来自MBP87 - 99免疫的LEW大鼠的T细胞在I - E背景下对MBP87 - 99有反应，而MBP87 - 99免疫的DA大鼠的肽特异性反应是I - A限制的，尽管流式细胞仪分析表明DA大鼠同时表达I - A和I - E。DA大鼠对用PLP诱导的EAE也高度敏感；0.6 nmol对DA大鼠具有致脑炎性，但在LEW大鼠中不诱导临床EAE。尽管DA大鼠和LEW大鼠对EAE都高度敏感，但我们证明了在能够诱导该疾病的髓鞘表位阵列以及这两种大鼠品系之间这些表位的主要组织相容性复合体（MHC）限制方面存在显著差异。
