Role of APC in the selection of immunodominant T cell epitopes
| Autor: | C, Ma, P E, Whiteley, P M, Cameron, D C, Freed, A, Pressey, S L, Chen, B, Garni-Wagner, C, Fang, D M, Zaller, L S, Wicker, J S, Blum |
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| Rok vydání: | 1999 |
| Předmět: |
Antigen Presentation
Immunodominant Epitopes T-Lymphocytes Molecular Sequence Data Histocompatibility Antigens Class II Immunization Passive Antigen-Presenting Cells Epitopes T-Lymphocyte Immunoglobulins Cell Line Protein Structure Tertiary Mice Inbred C57BL Immunoglobulin kappa-Chains Mice HLA Antigens Immunoglobulin G Animals Humans Amino Acid Sequence Peptides Protein Binding |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 163(12) |
| ISSN: | 0022-1767 |
| Popis: | Following antigenic challenge, MHC-restricted T cell responses are directed against a few dominant antigenic epitopes. Here, evidence is provided demonstrating the importance of APC in modulating the hierarchy of MHC class II-restricted T cell responses. Biochemical analysis of class II:peptide complexes in B cells revealed the presentation of a hierarchy of peptides derived from the Ig self Ag. Functional studies of kappa peptide:class II complexes from these cells indicated that nearly 20-fold more of an immunodominant epitope derived from kappa L chains was bound to class II DR4 compared with a subdominant epitope from this same Ag. In vivo, T cell responses were preferentially directed against the dominant kappa epitope as shown using Ig-primed DR4 transgenic mice. The bias in kappa epitope presentation was not linked to differences in class II:kappa peptide-binding affinity or epitope editing by HLA-DM. Rather, changes in native Ag structure were found to disrupt presentation of the immunodominant but not the subdominant kappa epitope; Ag refolding restored kappa epitope presentation. Thus, Ag tertiary conformation along with processing reactions within APC contribute to the selective presentation of a hierarchy of epitopes by MHC class II molecules. |
| Databáze: | OpenAIRE |
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