Peptide-specific, TCR-alpha-driven, coreceptor-independent negative selection in TCR alpha-chain transgenic mice
Authors
Furmanski, Anna L.Bartok, Istvan
Chai, Jian-Guo
Singh, Yogesh
Ferreira, Cristina
Scott, Diane
Holland, Stephen J.
Bourdeaux, Christophe
Crompton, Tessa
Dyson, Julian
Issue Date
2010-01-06
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As 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.Citation
Furmanski 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.Publisher
American Association of ImmunologistsJournal
Journal of ImmunologyPubMed ID
19995903Additional Links
http://www.jimmunol.org/cgi/content/full/184/2/650Type
ArticleLanguage
enISSN
0022-1767ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.0902291
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