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

  • Sci Rep. 2017 Aug 30;7(1):9923. doi: 10.1038/s41598-017-10265-6.
Junyun Lai  1  2 ,  Joanna Ai Ling Choo  2 ,  Wei Jian Tan  1  2 ,  Chien Tei Too  1  2 ,  Min Zin Oo  1  2 ,  Manuel A Suter  1  2 ,  Fatimah Bte Mustafa  1  2 ,  Nalini Srinivasan  2 ,  Conrad En Zuo Chan  3 ,  Andrew Guo Xian Lim  1  2 ,  Youjia Zhong  1  2 ,  Soh Ha Chan  2 ,  Brendon J Hanson  3 ,  Nicholas R J Gascoigne  2 ,  Paul A MacAry  4  5
Affiliations
  • 1. Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore.
  • 2. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore.
  • 3. Defense Medical and Environmental Research Institute, DSO National Laboratories, Singapore, 117510, Singapore.
  • 4. Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 117456, Singapore. [email protected].
  • 5. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117545, Singapore. [email protected].
PMID: 28855662 DOI: 10.1038/s41598-017-10265-6
Abstract

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.

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