Competitive Inhibition In Vivo and Skewing of the T Cell Repertoire of Antigen-Specific CTL Priming by an Anti-Peptide-MHC Monoclonal Antibody
| Autor: | Michael A. Derby, Lisa F. Boyd, David H. Margulies, Igor M. Belyakov, Doo Hyun Chung, Jay A. Berzofsky, Jian Wang |
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| Rok vydání: | 2001 |
| Předmět: |
Cytotoxicity
Immunologic HIV Antigens Receptors Antigen T-Cell alpha-beta T cell Immunology Epitopes T-Lymphocyte Priming (immunology) chemical and pharmacologic phenomena Biology Lymphocyte Activation Major histocompatibility complex Binding Competitive Epitope HIV Envelope Protein gp160 Mice medicine Animals Humans Immunology and Allergy Avidity Lymphocyte Count Antibodies Blocking Histocompatibility Antigen H-2D Mice Inbred BALB C Stem Cells T-cell receptor H-2 Antigens Antibodies Monoclonal Virology Molecular biology CTL medicine.anatomical_structure Injections Intravenous biology.protein Oligopeptides Injections Intraperitoneal CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Immunology. 167:699-707 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.167.2.699 |
| Popis: | We have recently described a mAb, KP15, directed against the MHC-I/peptide molecular complex consisting of H-2Dd and a decamer peptide corresponding to residues 311–320 of the HIV IIIB envelope glycoprotein gp160. When administered at the time of primary immunization with a vaccinia virus vector encoding gp160, the mAb blocks the subsequent appearance of CD8+ CTL with specificity for the immunodominant Ag, P18-I10, presented by H-2Dd. This inhibition is specific for this particular peptide Ag; another H-2Dd-restricted gp160 encoded epitope from a different HIV strain is not affected, and an H-2Ld-restricted epitope encoded by the viral vector is also not affected. Using functional assays and specific immunofluorescent staining with multivalent, labeled H-2Dd/P18-I10 complexes (tetramers), we have enumerated the effects of blocking of priming on the subsequent appearance, avidity, and TCR Vβ usage of Ag-specific CTL. Ab blocking skews the proportion of high avidity cells emerging from immunization. Surprisingly, Vβ7-bearing Ag-specific TCR are predominantly inhibited, while TCR of several other families studied are not affected. The ability of a specific MHC/peptide mAb to inhibit and divert the CD8+ T cell response holds implications for vaccine design and approaches to modulate the immune response in autoimmunity. |
| Databáze: | OpenAIRE |
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