Mäkelä M J
Department of Virology, University of Turku, Finland.
J Neurol Sci. 1989 Apr;90(2):239-46. doi: 10.1016/0022-510x(89)90105-6.
Antibodies to different antigenic sites on measles virus (MV) surface proteins were examined in sera from 34 HLA-typed age- and sex-matched pairs of multiple sclerosis (MS) patients and control subjects by a previously developed competitive enzyme immunoassay in which human sera and monoclonal MV-specific antibodies compete for binding to the same antigen. Antibodies specific to 4 partly overlapping sites on the haemagglutinin protein and two sites on the fusion protein of MV were measured in addition to previously determined total antibody titres and antibody levels were compared between groups. MS patients had significantly higher levels of antibodies in six out of seven comparisons. Both the MS and the control group were further divided to subgroups with HLA-Dw2, -Dw1, -A2, -A3 and -B7 histocompatibility antigens and MV antibody levels in these groups were compared. The presence of the HLA-A2 or -A3 antigen did not have a significant effect on the antibody levels but both the HLA-Dw2 and -B7 antigens were associated with elevated antibody levels to antigenic sites defined by monoclonal antibodies. This was also supported by higher frequencies of these alleles in subgroups with high antibody titre both in MS patients and controls. Moreover, presence of Dw1 antigen was associated with lower mean titres especially against the fusion protein in control patients. The findings indicate that HLA antigens can control immune response to separate sites on a protein antigen either directly as immune response genes or through linkage to other genes.
通过先前开发的竞争性酶免疫测定法,检测了34对年龄和性别匹配的多发性硬化症(MS)患者及对照受试者血清中针对麻疹病毒(MV)表面蛋白不同抗原位点的抗体。在该测定法中,人血清和单克隆MV特异性抗体竞争结合同一抗原。除了先前测定的总抗体滴度外,还检测了针对MV血凝素蛋白上4个部分重叠位点以及融合蛋白上2个位点的特异性抗体,并比较了两组之间的抗体水平。在7项比较中的6项中,MS患者的抗体水平显著更高。MS组和对照组进一步分为具有HLA - Dw2、- Dw1、- A2、- A3和- B7组织相容性抗原的亚组,并比较了这些组中的MV抗体水平。HLA - A2或- A3抗原的存在对抗体水平没有显著影响,但HLA - Dw2和- B7抗原均与针对单克隆抗体所定义抗原位点的抗体水平升高有关。MS患者和对照组中抗体滴度高的亚组中这些等位基因的频率较高也支持了这一点。此外,Dw1抗原的存在与较低的平均滴度相关,尤其是对照患者中针对融合蛋白的平均滴度。这些发现表明,HLA抗原可以作为免疫反应基因直接控制对蛋白质抗原上不同位点的免疫反应,或者通过与其他基因的连锁来控制。