Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands;
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands.
J Immunol. 2021 Apr 15;206(8):1957-1965. doi: 10.4049/jimmunol.2001405. Epub 2021 Mar 10.
MHC class I molecules play an important role in adaptive immune responses against intracellular pathogens. These molecules are highly polymorphic, and many allotypes have been characterized. In a transplantation setting, a mismatch between MHC allotypes may initiate an alloimmune response. Rhesus macaques (, ) are valuable as a preclinical model species in transplantation research as well as to evaluate the safety and efficacy of vaccine candidates. In both lines of research, the availability of nonhuman primate MHC-reactive mAbs may enable in vitro monitoring and detection of presence of particular Mamu molecules. In this study, we screened a collection of thoroughly characterized HLA class I-specific human mAbs for cross-reactivity with rhesus macaque MHC class I allotypes. Two mAbs, OK4F9 and OK4F10, recognize an epitope that is defined by isoleucine (I) at amino acid position 142 that is present on the Indian rhesus macaque Mamu-B008:01 allotype, which is an allotype known to be associated with elite control of SIV replication. The reactive pattern of a third mAb, MUS4H4, is more complex and includes an epitope shared on Mamu-A205:01 and -B*001:01-encoded Ags. This is the first description, to our knowledge, of human HLA-reactive mAbs that can recognize Mamu allotypes, and these can be useful tools for in vitro monitoring the presence of the relevant allelic products. Moreover, OK4F9 and OK4F10 can be powerful mAbs for application in SIV-related research.
MHC I 类分子在针对细胞内病原体的适应性免疫反应中发挥重要作用。这些分子高度多态性，许多同种异型已被描述。在移植环境中，MHC 同种异型不匹配可能引发同种异体免疫反应。恒河猴（Macaca mulatta）作为移植研究中的临床前模型物种以及评估疫苗候选物的安全性和有效性具有重要价值。在这两个研究领域中，非人类灵长类 MHC 反应性 mAb 的可用性可能使体外监测和检测特定 Mamu 分子的存在成为可能。在这项研究中，我们筛选了一组合适的 HLA I 类特异性人 mAb，以检测其与恒河猴 MHC I 同种异型的交叉反应性。两种 mAb，OK4F9 和 OK4F10，识别由氨基酸位置 142 上的异亮氨酸（I）定义的表位，该表位存在于印度恒河猴 Mamu-B008:01 同种异型上，该同种异型与 SIV 复制的精英控制有关。第三种 mAb，MUS4H4 的反应模式更为复杂，包括在 Mamu-A205:01 和 -B*001:01-编码的 Ag 上共享的表位。据我们所知，这是首次描述可识别 Mamu 同种异型的人类 HLA 反应性 mAb，这些 mAb 可用于体外监测相关等位基因产物的存在。此外，OK4F9 和 OK4F10 可以成为 SIV 相关研究中应用的强大 mAb。
