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

Content Provider	PubMed Central
Author	Clement, Mathew Ladell, Kristin Julia, Ekeruche-makinde Miles, John J. Edwards, Emily S. J. Dolton, Garry Williams, Tamsin Schauenburg, Andrea J. A. Cole, David K. Lauder, Sarah N. Gallimore, Awen M. Godkin, Andrew J. Burrows, Scott R. Price, David A. Sewell, Andrew K. Wooldridge, Linda
Abstract	CD8+ T-cells recognize immunogenic 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 effects on antigen sensitivity. Anti-CD8 antibodies 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 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 CD8+ T-cell clones with a total of five different specificities. Six out of seven anti-human CD8 antibodies tested did not activate CD8+ T-cells. In contrast, one anti-human CD8 antibody, 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 antigen-specific CD8+ T-cells. The anti-mouse CD8 antibodies, 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 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 CD8+ T-cell signalling.
Related Links	http://dx.doi.org/10.4049/jimmunol.1003941
Ending Page	663
Page Count	10
Starting Page	654
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	2
Volume Number	187
Language	English
Publisher Date	2011-07-15
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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