T Cell Activity Correlates with Oligomeric Peptide-Major Histocompatibility Complex Binding on T Cell Surface
| Autor: | Douglas J. Loftus, Mohamed Saad, Debora Donnini, Rui Zhao, Edward J. Collins, Jennifer Buslepp, Ettore Appella |
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| Rok vydání: | 2001 |
| Předmět: |
Models
Molecular Time Factors Protein Conformation T-Lymphocytes T cell Molecular Sequence Data chemical and pharmacologic phenomena Streptamer Crystallography X-Ray Ligands Major histocompatibility complex Biochemistry Mice HLA-A2 Antigen MHC class I medicine Animals Humans Cytotoxic T cell Biotinylation Amino Acid Sequence Antigen-presenting cell Molecular Biology Dose-Response Relationship Drug biology Cell Membrane Histocompatibility Antigens Class I T-cell receptor Cell Biology Flow Cytometry Molecular biology Recombinant Proteins Kinetics Phenotype Spectrometry Fluorescence medicine.anatomical_structure biology.protein Peptides Dimerization CD8 Protein Binding T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Biological Chemistry. 276:47320-47328 |
| ISSN: | 0021-9258 |
| Popis: | Recognition of virally infected cells by CD8+ T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the rejection of transplanted organs from the same species (allotransplant) or different species (xenotransplant). AHIII12.2 is a murine T cell clone that recognizes the xenogeneic (human) class I MHC HLA-A2.1 molecule (A2) and the syngeneic murine class I MHC H-2 D(b) molecule (D(b)). Recognition of both A2 and D(b) are peptide-dependent, and the sequences of the peptides recognized have been determined. Alterations in the antigenic peptides bound to A2 cause large changes in AHIII12.2 T cell responsiveness. Crystal structures of three representative peptides (agonist, null, and antagonist) bound to A2 partially explain the changes in AHIII12.2 responsiveness. Using class I pMHC octamers, a strong correlation is seen between T cell activity and the affinity of pMHC complexes for the T cell receptor. However, contrary to previous studies, we see similar half-lives for the pMHC multimers bound to the AHIII12.2 cell surface. |
| Databáze: | OpenAIRE |
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