TCR-like antibodies mediate complement and antibody-dependent cellular cytotoxicity against Epstein-Barr virus-transformed B lymphoblastoid cells expressing different HLA-A*02 microvariants.

Autor: Lai J; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Choo JAL; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Tan WJ; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Too CT; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Oo MZ; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Suter MA; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Mustafa FB; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Srinivasan N; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Chan CEZ; Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore, 117510, Singapore., Lim AGX; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Zhong Y; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Chan SH; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., Hanson BJ; Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore, 117510, Singapore., Gascoigne NRJ; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore., MacAry PA; Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore. paul_macary@nuhs.edu.sg.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore. paul_macary@nuhs.edu.sg.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Aug 30; Vol. 7 (1), pp. 9923. Date of Electronic Publication: 2017 Aug 30.
DOI: 10.1038/s41598-017-10265-6
Abstrakt: Epstein-Barr virus (EBV) is a common gammaherpesvirus associated with various human malignancies. Antibodies with T cell receptor-like specificities (TCR-like mAbs) provide a means to target intracellular tumor- or virus-associated antigens by recognising their processed peptides presented on major histocompatibility complex (MHC) class I (pMHC) complexes. These antibodies are however thought to be relevant only for a single HLA allele. Here, we show that HLA-A*02:01-restricted EBV antigenic peptides EBNA1 562-570 , LMP1 125-133 and LMP2A 426-434 display binding degeneracy towards HLA-A*02 allelic microvariants, and that these pMHC complexes are recognised by anti-EBV TCR-like mAbs E1, L1 and L2 raised in the context of HLA-A*02:01. These antibodies bound endogenously derived pMHC targets on EBV-transformed human B lymphoblastoid cell lines expressing A*02:01, A*02:03, A*02:06 and A*02:07 alleles. More importantly, these TCR-like mAbs mediated both complement-dependent and antibody-dependent cellular cytotoxicity of these cell lines in vitro. This finding suggests the utility of TCR-like mAbs against target cells of closely related HLA subtypes, and the potential applicability of similar reagents within populations of diverse HLA-A*02 alleles.
Databáze: MEDLINE
Externí odkaz: