Clonotypically similar hybrid T cell receptors can exhibit markedly different surface expression, antigen specificity and cross-reactivity

被引:2
作者
Motozono, C. [1 ,2 ]
Bridgeman, J. S. [2 ]
Price, D. A. [2 ]
Sewell, A. K. [2 ]
Ueno, T. [1 ,3 ]
机构
[1] Kumamoto Univ, Ctr AIDS Res, Honjo, Kumamoto 8600811, Japan
[2] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales
[3] Kumamoto Univ, Int Res Ctr Med Res, Honjo, Kumamoto 8600811, Japan
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
CD8(+) T cells; CDR3; HIV; TCR; ENHANCED ANTITUMOR-ACTIVITY; CANCER REGRESSION; IMMUNE ESCAPE; TCR; PEPTIDE; RECOGNITION; DISPLAY; LYMPHOCYTES; SINGLE; RECONSTITUTION;
D O I
10.1111/cei.12610
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Emerging data indicate that particular major histocompatibility complex (MHC)-bound antigenic peptides can be recognized by identical or near-identical T cell receptors (TCRs) in different individuals. To establish the functional relevance of this phenomenon, we artificially paired and chains from closely related TCRs specific for the human leucocyte antigen (HLA)-B*35:01-restricted HIV-1 negative regulatory factor (Nef)-derived epitope VY8 (VPLRPMTY, residues 74-81). Several hybrid TCRs generated in this manner failed to express at the cell surface, despite near homology with naturally isolated chain combinations. Moreover, a substantial proportion of those TCRs that did express lost specificity for the index VY8 peptide sequence. One such hybrid pair gained neo-variant specificity in the context of the VY8 backbone. Collectively, these data show that clonotypically similar TCRs can display profound differences in surface expression, antigen specificity and cross-reactivity with potential relevance for the control of mutable viruses.
引用
收藏
页码:560 / 570
页数:11
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