Anti-CD8 antibodies can trigger T-cell effector function in the absence of TCR engagement and improve pMHCI tetramer staining (113.28)

Abstract

Abstract Cytotoxic T lymphocytes (CTLs) recognize foreign peptides presented at the cell surface bound to major histocompatibility complex class I (MHCI) molecules. Antigen recognition involves the binding of both T-cell receptor (TCR) and CD8 co-receptor to the same peptide-MHCI (pMHCI) ligand. Specificity is determined by the TCR, whereas CD8 mediates an effect on antigen sensitivity. Anti-CD8 antibodies have been used extensively in previous studies to examine the role of CD8 in CTL activation. However, it is unclear from the literature whether anti-CD8 antibodies per se are capable of inducing effector function. Here, we report on the ability of seven monoclonal anti-human CD8 antibodies to activate six human CTL clones with a total of five different specificities. Six out of seven anti-human CD8 antibodies tested did not activate CTLs. In contrast, one anti-human CD8 antibody, OKT8, induced effector function in all CTLs examined. Moreover, OKT8 was found to enhance TCR/pMHCI on-rates and, as a consequence, could be used to improve pMHCI tetramer staining. The observed heterogeneity in the ability of anti-CD8 antibodies to trigger T-cell effector function provides an explanation for the apparent incongruity observed in previous studies and should be taken into consideration when interpreting results generated with these reagents. Furthermore, the ability of antibody-mediated CD8 engagement to deliver an activation signal underscores the importance of CD8 in CTL signalling.