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

2017; Nature Portfolio; Volume: 7; Issue: 1 Linguagem: Inglês

10.1038/s41598-017-10265-6

2045-2322

Junyun Lai, Joanna Ai Ling Choo, Wei Jian Tan, Chien Tei Too, Min Zin Oo, Manuel Adrian Suter, Fatimah Bte Mustafa, Nalini Srinivasan, Conrad En Zuo Chan, Andrew Guo Xian Lim, Youjia Zhong, Soh Ha Chan, Brendon J. Hanson, Nicholas R. J. Gascoigne, Paul A. MacAry,

Immunotherapy and Immune Responses

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 EBNA1562-570, LMP1125-133 and LMP2A426-434 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.