Anti-coreceptor antibodies profoundly affect staining with peptide-MHC class I and class II tetramers

Wooldridge, Linda, Scriba, Thomas J., Milicic, Anita, Laugel, Bruno Frederic, Gostick, Emma, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Phillips, Rodney E. and Sewell, Andrew ORCID: https://orcid.org/0000-0003-3194-3135 2006. Anti-coreceptor antibodies profoundly affect staining with peptide-MHC class I and class II tetramers. European Journal of Immunology 36 (7) , pp. 1847-1855. 10.1002/eji.200635886

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	CD4 ; CD8 ; Peptide-MHC tetramers ; T cell activation ; T cell receptors
ISSN:	15214141
Last Modified:	06 May 2023 02:22
URI:	https://orca.cardiff.ac.uk/id/eprint/343

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