Wiertz E J, Delvig A, Donders E M, Brugghe H F, van Unen L M, Timmermans H A, Achtman M, Hoogerhout P, Poolman J T
Laboratory of Vaccine Development and Immune Mechanisms, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Infect Immun. 1996 Jan;64(1):298-304. doi: 10.1128/iai.64.1.298-304.1996.
Former studies have shown that the class 5 outer membranes proteins (Opa and Opc proteins) of Neisseria meningitidis are at least as immunogenic as meningococcal porin proteins. High antibody titers to class 5 proteins have been observed in sera obtained during convalescence after meningococcal infection. A strong increase in anti-class 5 antibodies has also been observed in vaccinees who received a meningococcal outer membrane vesicle preparation. The enhanced B-cell response to class 5 proteins may be due to the presence of immunodominant helper T-cell epitopes in these proteins. In order to investigate this hypothesis, we tested purified Opa, Opc, and class 1 proteins for recognition by human T cells. a hierarchy of T-cell immunogenicity was observed among the outer membrane proteins, the Opa protein being more immunogenic than the other proteins. In most cases, the proliferative responses elicited by Opc were higher than the responses observed for the class 1 protein. The epitopes recognized by the immune T cells were identified by using overlapping synthetic peptides spanning the protein sequences of OpaB, Opa5d, and Opc.
以往的研究表明,脑膜炎奈瑟菌的5类外膜蛋白(Opa和Opc蛋白)的免疫原性至少与脑膜炎球菌孔蛋白相当。在脑膜炎球菌感染后的恢复期血清中观察到针对5类蛋白的高抗体滴度。在接受脑膜炎球菌外膜囊泡制剂的疫苗接种者中也观察到抗5类抗体的显著增加。对5类蛋白增强的B细胞反应可能是由于这些蛋白中存在免疫显性辅助性T细胞表位。为了研究这一假设,我们检测了纯化的Opa、Opc和1类蛋白被人T细胞识别的情况。在外膜蛋白中观察到T细胞免疫原性的层次结构,Opa蛋白比其他蛋白更具免疫原性。在大多数情况下,Opc引发的增殖反应高于1类蛋白所观察到的反应。通过使用跨越OpaB、Opa5d和Opc蛋白序列的重叠合成肽来鉴定免疫T细胞识别的表位。