Cole, David ![]() ![]() |
Abstract
Human CD8 is a T cell coreceptor, which binds to pHLA I and plays a pivotal role in the activation of cytotoxic T lymphocytes. Soluble recombinant CD8 αα has been shown to antagonize T cell activation, both in vitro and in vivo. However, because of a very low affinity for pHLA I, high concentrations of soluble CD8 αα are required for efficient inhibition. Based upon our knowledge of the wild-type CD8/pHLA I structure, we have designed and produced a mutated form of soluble CD8 αα that binds to pHLA I with approximately fourfold higher affinity. We have characterized the binding of the high affinity CD8 mutant using surface plasmon resonance and determined its structure at 2.1 Å resolution using X-ray crystallography. The analysis of this structure suggests that the higher affinity is achieved by providing a larger side chain that allows for an optimal contact to be made between the HLA α3 loop and the mutated CDR-like loops of CD8.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Medicine Systems Immunity Research Institute (SIURI) |
Subjects: | R Medicine > R Medicine (General) |
Uncontrolled Keywords: | CD8; coreceptor; soluble protein; crystal structure; KD; protein engineering; immunotherapy; immune-suppressor. |
Publisher: | Wiley-Blackwell |
ISSN: | 0887-3585 |
Last Modified: | 25 Oct 2022 09:54 |
URI: | https://orca.cardiff.ac.uk/id/eprint/60460 |
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