Anti-CD8 Antibodies Can Trigger CD8+ T Cell Effector Function in the Absence of TCR Engagement and Improve Peptide–MHCI Tetramer Staining
Autor: | Awen Gallimore, David K. Cole, Garry Dolton, John J. Miles, David Price, Scott R. Burrows, Tamsin Williams, Kristin Ladell, Julia Ekeruche-Makinde, Emily S.J. Edwards, Andrea J. A. Schauenburg, Andrew K. Sewell, Andrew James Godkin, Linda Wooldridge, Mathew Clement, Sarah Nicol Lauder |
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Rok vydání: | 2011 |
Předmět: |
Cytotoxicity
Immunologic CD8 Antigens T cell Immunology Receptors Antigen T-Cell CD8-Positive T-Lymphocytes Biology Ligands Article Antibodies Immunophenotyping Antigen Tetramer HLA-A2 Antigen medicine Humans Immunology and Allergy Cytotoxic T cell Receptor HLA-A Antigens Staining and Labeling Effector T-cell receptor Surface Plasmon Resonance Molecular biology Clone Cells medicine.anatomical_structure Peptides CD8 Signal Transduction |
Zdroj: | The Journal of Immunology. 187:654-663 |
ISSN: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.1003941 |
Popis: | 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. |
Databáze: | OpenAIRE |
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