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Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Sci+Rep 2017 ; 7 (ä): ä Nephropedia Template TP
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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 #MMPMID28855662
Lai J; Choo JAL; Tan WJ; Too CT; Oo MZ; Suter MA; Mustafa FB; Srinivasan N; Chan CEZ; Lim AGX; Zhong Y; Chan SH; Hanson BJ; Gascoigne NRJ; MacAry PA
Sci Rep 2017[]; 7 (ä): ä PMID28855662show ga
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.