The Self-Directed T Cell Repertoire Against Mouse Lysozyme Reflects the Influence of the Hierarchy of Its Own Determinants and Can Be Engaged by a Foreign Lysozyme
| Autor: | K D, Moudgil, S, Southwood, A, Ametani, K, Kim, A, Sette, E E, Sercarz |
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| Rok vydání: | 1999 |
| Předmět: |
Mice
Inbred BALB C Binding Sites Injections Subcutaneous T-Lymphocytes Molecular Sequence Data Immunology H-2 Antigens Epitopes T-Lymphocyte Lymphocyte Activation Peptide Fragments Mice Inbred C57BL Mice Haplotypes Mice Inbred CBA Animals Immunology and Allergy Female Muramidase Amino Acid Sequence Antigens Chickens |
| Zdroj: | The Journal of Immunology. 163:4232-4237 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.163.8.4232 |
| Popis: | The T cell repertoire is shaped by the processes of positive and negative selection. We have previously shown that mice are tolerant to a native self-Ag, mouse lysozyme (ML), but they respond vigorously when challenged with different ML peptides (“cryptic” self-determinants). In this study, we have addressed the issue of the physiological significance of both the hierarchy (dominance/crypticity) of self-determinants within ML and the anti-cryptic, self (ML)-directed T cell repertoire. Our results demonstrate that there are several ML peptides that bind well to MHC but are totally nonimmunogenic when tested for proliferative T cell response and cytokine secretion: a subset of these peptides presumably represent the originally dominant self-determinants of ML, which have rendered the T cells tolerant during thymic selection. Other ML peptides, which bind well to MHC and are immunogenic, correspond to the cryptic determinants of ML: T cells against cryptic ML determinants escape tolerance induction. Thus, the mature T cell repertoire against ML bears the direct imprint of the hierarchy of self (ML)-determinants. Interestingly, hen egg white lysozyme could prime T cells in vivo that were cross-reactive with certain cryptic ML determinants, and vice versa, without requiring any coimmunization with the foreign lysozyme and ML peptide(s). Moreover, repeated, deliberate priming and expansion of T cells by hen egg white lysozyme immunization concomitantly enhanced T cell response to such cross-reactive ML determinants. This reciprocal self-foreign determinant cross-reactivity may play a previously unrecognized, but crucial, role in the expansion and diversification of self-reactive clones in the autoimmune response. |
| Databáze: | OpenAIRE |
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