Structural basis of the TCR-pHLA complex provides insights into the unconventional recognition of CDR3β in TCR cross-reactivity and alloreactivity
Dan San,
Jun Lei,
Yang Liu,
Baowei Jing,
Xiang Ye,
Pengcheng Wei,
Chonil Paek,
Yi Yang,
Jin Zhou,
Peng Chen,
Hongjian Wang,
Yongshun Chen,
Lei Yin
Affiliations
Dan San
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Jun Lei
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Yang Liu
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Baowei Jing
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Xiang Ye
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Pengcheng Wei
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Chonil Paek
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Yi Yang
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Jin Zhou
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Peng Chen
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Hongjian Wang
State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Yongshun Chen
Corresponding author.; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Lei Yin
Corresponding author.; State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China
Evidence shows that some class I human leucocyte antigen (HLA) alleles are related to durable HIV controls. The T18A TCR, which has the alloreactivity between HLA-B∗42:01 and HLA-B∗81:01 and the cross-reactivity with different antigen mutants, can sustain long-term HIV controls. Here the structural basis of the T18A TCR binding to the immunodominant HIV epitope TL9 (TPQDLNTML180-188) presented by HLA-B∗42:01 was determined and compared to T18A TCR binding to the TL9 presented by the allo-HLA-B∗81:01. For differences between HLA-B∗42:01 and HLA-B∗81:01, the CDR1α and CDR3α loops adopt a small rearrangement to accommodate them. For different conformations of the TL9 presented by different HLA alleles, not like the conventional recognition of CDR3s to interact with peptide antigens, CDR3β of the T18A TCR shifts to avoid the peptide antigen but intensively recognizes the HLA only, which is different with other conventional TCR structures. Featured sequence pairs of CDR3β and HLA might account for this and were additionally found in multiple other diseases indicating the popularity of the unconventional recognition pattern which would give insights into the control of diseases with epitope mutating such as HIV.
