Deep sequencing of the T cell receptor β repertoire reveals signature patterns and clonal drift in atherosclerotic plaques and patients

// Zongwei Lin 1,* , Shao Qian 3,* , Yan Gong 2,* , Jianwei Ren 6 , Lixia Zhao 4 , Dongxiao Wang 5 , Xiaowei Wang 1 , Yun Zhang 1 , Zhe Wang 2 and Qunye Zhang 1 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, and The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China 2 Division of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China 3 Department of Women Health Care, Jinan Maternity and Child Care Hospital, Jinan, China 4 Pharmacy Department of Shandong Medical College, Jinan, China 5 Department of Pharmacy, Chinese PLA General Hospital, Beijing, China 6 Health Division of Guard Bureau, General Staff Department of Chinese PLA, Beijing, China * These authors have equally contributed to this study Correspondence to: Qunye Zhang, email: // Zhe Wang, email: // Keywords : T cell receptor β, atherosclerosis, immune repertoire, next-generation DNA sequencing, complement determining region 3, Immunology and Microbiology Section, Immune response, Immunity Received : April 12, 2017 Accepted : June 18, 2017 Published : August 03, 2017 Abstract The T cell receptor (TCR) β repertoire directly reflects the status of T cell function. Meanwhile, the immune/inflammatory responses regulated by T cells are the critical determinants of atherosclerosis development. However, due to technical limitations, the composition and molecular characteristics of the TCR repertoire in atherosclerotic patients have not been fully elucidated. In the present study, we use powerful immune repertoire sequencing technology to study this issue. Results show that the utilization of V and/or J genes and the diversity of TCRβ repertoire in atherosclerotic plaques are significantly reduced compared to those in the peripheral blood of normal subjects and atherosclerotic patients. The frequencies of the common T cell clones with certain lengths of the complement determining region 3 regions are notably different among all groups. The high-frequency common clones are also increased in the atherosclerotic plaques compared to that in the other two groups. The expansion of several T cell clonotypes (V29-1J2-1, V20-1J1-6, V6-3J2-7 and V11-2J2-2) is validated in atherosclerotic patients. In short, this study reveals that the diversity of TCR β repertoire significantly decreases in atherosclerotic plaques, probably because of the reduced utilization of VJ genes and marked expansion of some T cell subclones. It provides the basis for understanding the roles of T lymphocytes in the pathogenesis of atherosclerosis.