Trends in Genetics ( IF 11.4 ) Pub Date : 2020-10-21 , DOI: 10.1016/j.tig.2020.10.001 Pierre Pontarotti 1 , Laurent Abi-Rached 2 , Jung-Hua Yeh 3 , Julien Paganini 4
The relationship between human genetic variation and disease has not been fully elucidated. According to the present view on infectious diseases pathogen resistance is linked to human leukocyte antigen (HLA) class I/II variants and their individual capacity to present pathogen-derived peptides. Yet, T cell education in the thymus occurs through negative and positive selection, and both processes are controlled by a combination of HLA class I/II variants and peptides from the self. Therefore, the capacity of given HLA class I/II variants to bind pathogen-derived peptides is only one part of the selective process to generate effective immune responses. We thus propose that peptidome variation contributes to shaping T cell receptor (TCR) repertoires and hence individual immune responses, and that this variation represents inherent modulator epitopes.
中文翻译:
自身肽组变异塑造个体免疫反应
人类遗传变异与疾病之间的关系尚未完全阐明。根据目前关于传染病病原体抗性的观点,人类白细胞抗原 (HLA) I/II 类变体及其呈递病原体衍生肽的个体能力有关。然而,胸腺中的 T 细胞教育是通过负选择和正选择发生的,这两个过程都由 HLA I/II 类变体和来自自身的肽的组合控制。因此,给定的 HLA I/II 类变体结合病原体衍生肽的能力只是产生有效免疫反应的选择性过程的一部分。因此,我们提出肽组变异有助于塑造 T 细胞受体 (TCR) 库,从而有助于形成个体免疫反应,并且这种变异代表了固有的调节剂表位。