Peptide-specific, TCR-alpha-driven, coreceptor-independent negative selection in TCR alpha-chain transgenic mice
| Autor: | Christophe Bourdeaux, Tessa Crompton, Anna L. Furmanski, Cristina Ferreira, Jian-Guo Chai, Julian Dyson, Stephen J. Holland, Diane Scott, Yogesh Singh, Istvan Bartok |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male T cell Receptors Antigen T-Cell alpha-beta Immunology Mice Transgenic T-Cell Antigen Receptor Specificity Thymus Gland CD8-Positive T-Lymphocytes Major histocompatibility complex Clonal deletion Negative selection Mice Sex Factors MHC class I medicine Immunology and Allergy Animals Histone Demethylases biology T-cell receptor Proteins Molecular biology medicine.anatomical_structure biology.protein Female Peptides Alpha chain CD8 Spleen Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 184(2) |
| ISSN: | 1550-6606 |
| Popis: | As thymocytes differentiate, Ag sensitivity declines, with immature CD4−CD8− double-negative (DN) cells being most susceptible to TCR signaling events. We show that expression of αβTCR from the DN3 stage lowers the threshold for activation, allowing recognition of MHC peptides independently of the TCR β-chain and without either T cell coreceptor. The MHC class I-restricted C6 TCR recognizes the Y-chromosome–derived Ag HYKkSmcy. Positive selection in C6 αβTCR females is skewed to the CD8 compartment, whereas transgenic male mice exhibit early clonal deletion of thymocytes. We investigated the effect of the HYKkSmcy complex on developing thymocytes expressing the C6 TCR α-chain on a TCR-α−/− background. On the original selecting haplotype, the skew to the CD8 lineage is preserved. This is MHC dependent, as the normal bias to the CD4 subset is seen on an H2b background. In male H2k C6 α-only mice, the presence of the HYKkSmcy complex leads to a substantial deletion of thymocytes from the DN subset. This phenotype is replicated in H2k C6 α-only female mice expressing an Smcy transgene. Deletion is not dependent on the β variable segment of the C6 TCR or on a restricted TCR-β repertoire. In contrast, binding of HYKkSmcy and Ag-specific activation of mature CD8+ T cells is strictly dependent on the original C6 β-chain. These data demonstrate that, in comparison with mature T cells, αβTCR+ immature thymocytes can recognize and transduce signals in response to specific MHC-peptide complexes with relaxed binding requirements. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|