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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / metabolism*
  • Antibody-Dependent Cell Cytotoxicity
  • Cell Line, Tumor
  • Genetic Variation
  • HLA-A2 Antigen / chemistry
  • HLA-A2 Antigen / genetics*
  • HLA-A2 Antigen / immunology
  • Herpesviridae Infections / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Models, Molecular
  • Peptide Fragments / metabolism
  • Receptors, Antigen, T-Cell / metabolism*

Substances

  • Antibodies, Monoclonal
  • HLA-A*02 antigen
  • HLA-A2 Antigen
  • Peptide Fragments
  • Receptors, Antigen, T-Cell