| First Author | Ma C | Year | 1999 |
| Journal | J Immunol | Volume | 163 |
| Issue | 12 | Pages | 6413-23 |
| PubMed ID | 10586031 | Mgi Jnum | J:96131 |
| Mgi Id | MGI:3529549 | Doi | 10.4049/jimmunol.163.12.6413 |
| Citation | Ma C, et al. (1999) Role of APC in the selection of immunodominant T cell epitopes. J Immunol 163(12):6413-23 |
| abstractText | 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. |
