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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Anti-coreceptor antibodies profoundly affect staining with peptide-MHC class I and class II tetramers
European Journal of Immunology, Volume 36, No. 7, Year 2006
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Description
The T cell coreceptors CD8 and CD4 bind to invariable regions of peptide-MHC class I (pMHCI) and class II (pMHCII) molecules, respectively, and facilitate antigen recognition by a number of mechanisms. It is established that some antibodies (Ab) specific for the CD8 molecule, which stabilizes TCR/pMHCI interactions, can alter the binding of pMHCI tetramers to cell surface TCR. In contrast, the extremely weak pMHCII/CD4 interaction does not stabilize TCR/pMHCII interactions or contribute to cognate tetramer binding; consequently, it is assumed that anti-CD4 Ab do not affect pMHCII binding. Here, we used a panel of point-mutated HLA A2 molecules with a range of affinities for CD8 spanning over three orders of magnitude to demonstrate that anti-CD8 Ab-mediated inhibition of pMHCI tetramer binding and cognate T cell activation correlates directly with the strength of the pMHCI/CD8 interaction. Further, some anti-CD4 Ab were found to block pMHCII tetramer binding; these effects were also paralleled in T cell activation assays. In sum, these data challenge the assertion that anti-coreceptor Ab exert their effects on T cell activation and pMHC binding solely by blocking pMHC/coreceptor interactions. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Authors & Co-Authors
Scriba, Thomas J.
United Kingdom, Oxford
Nuffield Department of Medicine
Milicic, Anita
United Kingdom, Oxford
Nuffield Department of Medicine
Gostick, Emma
United Kingdom, Oxford
Nuffield Department of Medicine
Price, David Ashley
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Phillips, Rodney E.
United Kingdom, Oxford
Nuffield Department of Medicine
Sewell, Andrew Kelvin
United Kingdom, Oxford
Nuffield Department of Medicine
Statistics
Citations: 21
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1002/eji.200635886
ISSN:
00142980