Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 37, Issue 5, Pages 1323-1333Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/eji.200636765
Keywords
CD8; cytotoxic T cells; MHC class I; T cell activation; tumor immunity
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Funding
- MRC [MC_U137884181, G0501963] Funding Source: UKRI
- Medical Research Council [G0501963, MC_U137884181] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- Medical Research Council [G0501963, MC_U137884181] Funding Source: researchfish
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CD8(+) cytotoxic T lymphocytes (CTL) are key determinants of immunity to intracellular pathogens and neoplastic cells. Recognition of specific antigens in the form of peptide-MHC class I complexes (pMHCI) presented on the target cell surface is mediated by T cell receptor (TCR) engagement. The CD8 coreceptor binds to invariant domains of pMHCI and facilitates antigen recognition. Here, we investigate the biological effects of a Q115E substitution in the a2 domain of human leukocyte antigen (HLA)-A*0201 that enhances CD8 binding by, -50% without altering TCR/pMHCI interactions. Soluble and cell surface-expressed forms of Q115E HLA-A*0201 exhibit enhanced recognition by CTL without loss of specificity. These CD8-enhanced antigens induce greater CD3 chain phosphorylation in cognate CTL leading to substantial increases in cytokine production, proliferation and priming of naive T cells. This effect provides a fundamental new mechanism with which to. enhance cellular immunity to specific T cell antigens.
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