Structural Engineering of pMHC Reagents for T Cell Vaccines and Diagnostics
| Autor: | Steven M. Truscott, Lonnie Lybarger, Daved H. Fremont, Ted H. Hansen, Janet M. Connolly, Vesselin Mitaksov |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular T-Lymphocytes T cell Clinical Biochemistry Molecular Conformation Receptors Antigen T-Cell chemical and pharmacologic phenomena Computational biology Crystallography X-Ray Major histocompatibility complex Biochemistry Article Epitope Major Histocompatibility Complex Epitopes Mice 03 medical and health sciences 0302 clinical medicine Immune system Antigen Diagnosis Drug Discovery MHC class I medicine Animals Cytotoxic T cell MOLIMMUNO Molecular Biology 030304 developmental biology Pharmacology Vaccines 0303 health sciences biology T-cell receptor General Medicine Virology 3. Good health CHEMBIO medicine.anatomical_structure biology.protein Molecular Medicine Peptides 030215 immunology |
| Zdroj: | Chemistry & Biology. 14:909-922 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/j.chembiol.2007.07.010 |
| Popis: | MHC class I peptide complexes (pMHC) are routinely used to enumerate T cell populations, and are currently being evaluated as vaccines to tumors and specific pathogens. Herein we describe the structures of three generations of single-chain pMHC progressively designed for the optimal presentation of covalently associated epitopes. Our ultimate and novel design employs a versatile disulfide trap between an invariant MHC residue and a short C-terminal peptide extension. This general strategy is non-disruptive of native pMHC conformation and T cell receptor engagement. Indeed, cell surface expressed MHC complexes with disulfide-trapped epitopes are refractory to peptide exchange suggesting they will make safe and effective vaccines. Furthermore, we find that disulfide-trap stabilized, recombinant pMHC reagents reliably detect polyclonal CD8 T cell populations as proficiently as conventional reagents, and are thus well-suited to monitor or modulate immune responses during pathogenesis. |
| Databáze: | OpenAIRE |
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