Peptide-specific, TCR-alpha-driven, coreceptor-independent negative selection in TCR alpha-chain transgenic mice
AuthorsFurmanski, Anna L.
Holland, Stephen J.
MetadataShow full item record
AbstractAs thymocytes differentiate, Ag sensitivity declines, with immature CD4-CD8- double-negative (DN) cells being most susceptible to TCRsignaling events. We show that expression of alphabetaTCR from the DN3 stage lowers the threshold for activation, allowing recognition of MHC peptides independently of the TCR beta-chain and without either T cell coreceptor. The MHC class I-restricted C6 TCR recognizes the Y-chromosome-derived Ag HYK(k)Smcy. Positive selection in C6 alphabetaTCR females is skewed to the CD8 compartment, whereas transgenic male mice exhibit early clonal deletion of thymocytes. We investigated the effect of the HYK(k)Smcy complex on developing thymocytes expressing the C6 TCR alpha-chain on a TCR-alpha(-/-) 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 alpha-only mice, the presence of the HYK(k)Smcy complex leads to a substantial deletion of thymocytes from the DN subset. This phenotype is replicated in H2k C6 alpha-only female mice expressing an Smcy transgene. Deletion is not dependent on the beta variable segment of the C6 TCR or on a restricted TCR-beta repertoire. In contrast, binding of HYK(k)Smcy and Ag-specific activation of mature CD8+ T cells is strictly dependent on the original C6 beta-chain. These data demonstrate that, in comparison with mature T cells, alphabetaTCR+ immature thymocytes can recognize and transduce signals in response to specific MHC-peptide complexes with relaxed binding requirements.
CitationFurmanski AL, Bartok I, Chai J, Singh Y, Ferreira C, Scott D, Holland SJ, Bourdeaux C, Crompton T, Dyson J (2010) 'Peptide-specific, TCR-alpha-driven, coreceptor-independent negative selection in TCR alpha-chain transgenic mice', Journal of Immunology, 184 (2), pp.650-657.
PublisherAmerican Association of Immunologists
JournalJournal of Immunology
- Opposite CD4/CD8 lineage decisions of CD4+8+ mouse and rat thymocytes to equivalent triggering signals: correlation with thymic expression of a truncated CD8 alpha chain in mice but not rats.
- Authors: Mitnacht R, Bischof A, Torres-Nagel N, Hünig T
- Issue date: 1998 Jan 15
- Examination of thymic positive and negative selection by flow cytometry.
- Authors: Hu Q, Nicol SA, Suen AY, Baldwin TA
- Issue date: 2012 Oct 8
- The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes.
- Authors: Penninger JM, Sirard C, Mittrücker HW, Chidgey A, Kozieradzki I, Nghiem M, Hakem A, Kimura T, Timms E, Boyd R, Taniguchi T, Matsuyama T, Mak TW
- Issue date: 1997 Aug
- Early molecular events induced by T cell receptor (TCR) signaling in immature CD4+ CD8+ thymocytes: increased synthesis of TCR-alpha protein is an early response to TCR signaling that compensates for TCR-alpha instability, improves TCR assembly, and parallels other indicators of positive selection.
- Authors: Kearse KP, Takahama Y, Punt JA, Sharrow SO, Singer A
- Issue date: 1995 Jan 1
- The quantity of TCR signal determines positive selection and lineage commitment of T cells.
- Authors: Watanabe N, Arase H, Onodera M, Ohashi PS, Saito T
- Issue date: 2000 Dec 1