Mitchell L A, Décarie D, Tingle A J, Zrein M, Lacroix M
Department of Pathology, University of British Columbia, Vancouver, Canada.
Virus Res. 1993 Jul;29(1):33-57. doi: 10.1016/0168-1702(93)90124-6.
Relatively large (16-33 aa) synthetic peptides (SPs) representing defined sequences of rubella virus (RV) E1 and E2 envelope proteins were used in lymphocyte stimulation and enzyme immunoassays to map immunoreactive regions recognized by peripheral blood mononuclear cells (PBMNC) and serum antibodies from healthy RV-seropositive, RV-seronegative, and RV-vaccinated adults. Five distinct immunoreactive regions were identified in RV E1 protein, spanning residues (11-39), (154-179), (199-239), (226-277), and (389-412), which stimulated cellular responses in 29-83% of the subjects tested. Two SPs, E1(213-239) and E1(258-277) containing previously-identified virus neutralizing antibody domains, reacted with serum antibodies and also stimulated lymphoproliferation suggesting that these E1 sequences contain linked or overlapping B-and T-cell antigenic sites. The frequency and magnitude of cellular responses to E2 SPs were somewhat lower. SPs encompassing E2 residues (50-72), (140-199), and (244-263) stimulated lymphocyte responses in 28-64% of the subjects tested, while to a lesser degree, SPs within residues (1-36) were also stimulatory. E2 SPs within the regions (1-36), (151-170), and (244-263) also showed low levels of antibody reactivity with sera from RV-seropositive subjects. E2(244-263) which induced the highest level of response among the E2 SPs tested, was of interest due to previous reports of sequence homology of this RV region with human myelin and its potential immunopathogenic role in demyelinating autoimmune diseases. Identification of these potentially immunodominant regions of RV envelope proteins is an important first step in the rational design of new RV vaccines.
相对较大（16 - 33个氨基酸）的合成肽（SPs）代表风疹病毒（RV）E1和E2包膜蛋白的特定序列，用于淋巴细胞刺激试验和酶免疫测定，以定位健康的RV血清阳性、RV血清阴性和接种RV疫苗的成年人外周血单核细胞（PBMNC）和血清抗体识别的免疫反应区域。在RV E1蛋白中鉴定出五个不同的免疫反应区域，跨越残基（11 - 39）、（154 - 179）、（199 - 239）、（226 - 277）和（389 - 412），这些区域在29% - 83%的受试对象中刺激了细胞反应。两个SPs，E1(213 - 239)和E1(258 - 277)包含先前鉴定的病毒中和抗体结构域，与血清抗体反应并刺激淋巴细胞增殖，表明这些E1序列包含相连或重叠的B细胞和T细胞抗原位点。对E2 SPs的细胞反应频率和强度略低。包含E2残基（50 - 72）、（140 - 199）和（244 - 263）的SPs在28% - 64%的受试对象中刺激了淋巴细胞反应，而残基（1 - 36）内的SPs也有一定程度的刺激作用。区域（1 - 36）、（151 - 170）和（244 - 263）内的E2 SPs与RV血清阳性受试者的血清也显示出低水平的抗体反应性。E2(244 - 263)在测试的E2 SPs中诱导的反应水平最高，鉴于先前报道该RV区域与人髓磷脂的序列同源性及其在脱髓鞘自身免疫性疾病中的潜在免疫致病作用，该区域备受关注。鉴定RV包膜蛋白的这些潜在免疫显性区域是合理设计新型RV疫苗的重要第一步。
