Enhanced immunogenicity of CTL antigens through mutation of the CD8 binding MHC class I invariant region
| Autor: | Meir Glick, Sarah L. Hutchinson, Bruno Laugel, Andrew K. Sewell, Linda Wooldridge, Jonathan Vernazza, David Price, Fareed Mirza, Hugo A. van den Berg, Vincenzo Cerundolo, Jonathan M. Boulter, P. Rod Dunbar, Emma Gostick, Anna Lissina |
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| Rok vydání: | 2007 |
| Předmět: |
CD8 Antigens
T cell Molecular Sequence Data Immunology Antigen presentation Receptors Antigen T-Cell Epitopes T-Lymphocyte Priming (immunology) Cytotoxic T cells chemical and pharmacologic phenomena Lymphocyte Activation Transfection Immunomodulation 03 medical and health sciences 0302 clinical medicine Tumor immunity HLA-A2 Antigen MHC class I medicine Humans Immunology and Allergy Cytotoxic T cell Amino Acid Sequence Protein Structure Quaternary 030304 developmental biology Antigen Presentation 0303 health sciences HLA-A Antigens biology T cell activation T-cell receptor CD8 Surface Plasmon Resonance Molecular biology 3. Good health CTL medicine.anatomical_structure Mutation biology.protein T-Lymphocytes Cytotoxic 030215 immunology |
| Zdroj: | European Journal of Immunology |
| ISSN: | 1521-4141 0014-2980 |
| Popis: | 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 alpha2 domain of human leukocyte antigen (HLA)-A*0201 that enhances CD8 binding by approximately 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 zeta 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. |
| Databáze: | OpenAIRE |
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