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: | Manuel Adrian Suter, Nicholas R. J. Gascoigne, Chien Tei Too, Min Zin Oo, Conrad E.Z. Chan, Junyun Lai, Wei Jian Tan, Andrew Guo Xian Lim, Brendon J. Hanson, Soh Ha Chan, Joanna Ai Ling Choo, Paul A. MacAry, Fatimah Bte Mustafa, Nalini Srinivasan, Youjia Zhong |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Herpesvirus 4 Human T cell Receptors Antigen T-Cell lcsh:Medicine chemical and pharmacologic phenomena Human leukocyte antigen Major histocompatibility complex medicine.disease_cause Article 03 medical and health sciences Antigen Cell Line Tumor HLA-A2 Antigen medicine Humans lcsh:Science Antibody-dependent cell-mediated cytotoxicity Multidisciplinary biology T-cell receptor lcsh:R Antibody-Dependent Cell Cytotoxicity Antibodies Monoclonal Genetic Variation Herpesviridae Infections Virology Molecular biology Epstein–Barr virus Peptide Fragments HLA-A 030104 developmental biology medicine.anatomical_structure biology.protein lcsh:Q |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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