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Anti-CD8 antibodies can trigger CD8+ T cell effector function in the absence of TCR engagement and improve peptide-MHCI tetramer staining

Clement, Mathew, Ladell, Kristin Ingrid, Ekeruche, Julia, Miles, John James, Edwards, Emily, Dolton, Garry Michael, Williams, Tamsin, Schauenburg, Andrea J. A., Cole, David, Lauder, Sarah Nicol, Gallimore, Awen Myfanwy, Godkin, Andrew James, Burrows, Scott R., Price, David, Sewell, Andrew K. and Wooldridge, Linda 2011. Anti-CD8 antibodies can trigger CD8+ T cell effector function in the absence of TCR engagement and improve peptide-MHCI tetramer staining. The Journal of Immunology 187 (2) , pp. 654-663. 10.4049/jimmunol.1003941

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Abstract

CD8+ T cells recognize immunogenic peptides presented at the cell surface bound to MHCI molecules. Ag recognition involves the binding of both TCR and CD8 coreceptor to the same peptide–MHCI (pMHCI) ligand. Specificity is determined by the TCR, whereas CD8 mediates effects on Ag sensitivity. Anti-CD8 Abs have been used extensively to examine the role of CD8 in CD8+ T cell activation. However, as previous studies have yielded conflicting results, it is unclear from the literature whether anti-CD8 Abs per se are capable of inducing effector function. In this article, we report on the ability of seven monoclonal anti-human CD8 Abs to activate six human CD8+ T cell clones with a total of five different specificities. Six of seven anti-human CD8 Abs tested did not activate CD8+ T cells. In contrast, one anti-human CD8 Ab, OKT8, induced effector function in all CD8+ T cells examined. Moreover, OKT8 was found to enhance TCR/pMHCI on-rates and, as a consequence, could be used to improve pMHCI tetramer staining and the visualization of Ag-specific CD8+ T cells. The anti-mouse CD8 Abs, CT-CD8a and CT-CD8b, also activated CD8+ T cells despite opposing effects on pMHCI tetramer staining. The observed heterogeneity in the ability of anti-CD8 Abs 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 Ab-mediated CD8 engagement to deliver an activation signal underscores the importance of CD8 in CD8+ T cell signaling.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of First Compliant Deposit: 19 January 2018
Last Modified: 08 Feb 2018 21:07
URI: http://orca.cf.ac.uk/id/eprint/29862

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