a UQ Centre for Clinical Research , The University of Queensland , Brisbane , Queensland , Australia.
Int Rev Immunol. 2015;34(6):460-85. doi: 10.3109/08830185.2015.1027822. Epub 2015 May 13.
Current treatments for autoimmune diseases are typically non-specific anti-inflammatory agents that affect not only the autoreactive cells but also the parts of the immune system that are required to maintain health. There is a need for the development of antigen-specific therapeutic agents that can effectively prevent the autoimmune attack while leaving the rest of the immune system functioning as normal. The simplest way to achieve this is using the autoantigen itself as a tolerizing agent; however, there is some risk involved with administering a potentially pathogenic antigen. In this review, we focus instead on the development and use of modified T cell receptor (TCR) ligands, in which the peptide ligand is modified to change the response by the T cell from a disease inducing to a protective response, and still retain the antigen-specificity necessary to target the autoreactive T cells. We review the use of modified TCR ligands as therapeutic agents in animal models of autoimmunity and in human autoimmune disease, and finally consider how they need to be improved in order to use them effectively in patients with autoimmune disease.
目前治疗自身免疫性疾病的方法通常是非特异性抗炎药物，这些药物不仅会影响自身反应性细胞，还会影响维持免疫系统健康所需的部分。因此，需要开发能够有效预防自身免疫攻击而不影响免疫系统正常功能的抗原特异性治疗药物。最简单的方法是使用自身抗原作为耐受原；然而，给予潜在致病性抗原存在一定风险。在这篇综述中，我们转而关注改良 T 细胞受体（TCR）配体的开发和应用，其中改变肽配体，使 T 细胞的反应从诱导疾病转变为保护反应，同时保留靶向自身反应性 T 细胞所需的抗原特异性。我们综述了改良 TCR 配体作为自身免疫动物模型和人类自身免疫性疾病治疗药物的应用，并最终考虑了如何改进它们，以便在自身免疫性疾病患者中有效使用。
