Aix Marseille Université, IRD, APHM, MEPHI, IHU Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseille, France; SNC5039 CNRS, 19-21 Boulevard Jean Moulin, 13005 Marseille, France; XEGEN, 15 rue Dominique Piazza, 13420 Gemenos, France.
Aix Marseille Université, IRD, APHM, MEPHI, IHU Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseille, France; SNC5039 CNRS, 19-21 Boulevard Jean Moulin, 13005 Marseille, France.
Trends Genet. 2021 May;37(5):414-420. doi: 10.1016/j.tig.2020.10.001. Epub 2020 Oct 21.
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.
人类遗传变异与疾病之间的关系尚未完全阐明。根据目前对传染病病原体抗性的认识，病原体抗性与人类白细胞抗原（HLA）I/II 类变体及其个体呈现病原体衍生肽的能力有关。然而，胸腺中的 T 细胞发育是通过阴性和阳性选择发生的，这两个过程都受 HLA I/II 类变体和自身肽的组合控制。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，从而影响个体免疫反应，并且这种变异代表固有调节表位。
