Public T cell receptor beta-chains are not advantaged during positive selection
Furmanski, Anna L., Ferreira, Cristina, Bartok, Istvan, Dimakou, Sofia, Rice, Jason, Stevenson, Freda K., Millrain, Maggie M., Simpson, Elizabeth and Dyson, Julian (2008) Public T cell receptor beta-chains are not advantaged during positive selection. Journal of Immunology, 180, (2), 1029-1039.
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Studies of human and murine T cells have shown that public TCR beta-chain rearrangements can dominate the Ag-specific and naive repertoires of distinct individuals. We show that mouse T cells responding to the minor histocompatibility Ag HYD(b)Smcy share an invariant V beta 8.2-J beta 2.3 TCR gene rearrangement. The dominance of this rearrangement shows that it successfully negotiated thymic selection and was highly favored during clonal expansion in all animals examined. We hypothesized that such beta-chains are advantaged during thymic and/or peripheral selection and, as a result, may be over-represented in the naive repertoire. A sequencing study was undertaken to examine the diversity of V beta 8.2-J beta 2.3 CDR3 loops from naive T cell repertoires of multiple mice. Public TCR beta-chain sequences were identified across different repertoires and MHC haplotypes. To determine whether such public beta-chains are advantaged during thymic selection, individual chains were followed through T cell development in a series of novel bone marrow competition chimeras. We demonstrate that beta-chains were positively selected with similar efficiency regardless of CDR3 loop sequence. Therefore, the establishment and maintenance of public beta-chains in the periphery is predominantly controlled by post-thymic events through modification of the primary, thymus-derived TCR repertoire.
|Keywords:||time, mhc, genes, receptor, selection, mouse, t-cells, repertoire, antigen receptor, clonal expansion, gene, thymocytes, t-cell, transgenic mice, cells, lineage commitment, t cells, individuals, bone-marrow, thymic selection, terminal deoxynucleotidyl transferase, development,alpha, self-peptide, rearrangements, cell|
Q Science > QR Microbiology > QR180 Immunology
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||05 Sep 2008|
|Last Modified:||02 Mar 2012 12:52|
|Contributors:||Furmanski, Anna L. (Author)
Ferreira, Cristina (Author)
Bartok, Istvan (Author)
Dimakou, Sofia (Author)
Rice, Jason (Author)
Stevenson, Freda K. (Author)
Millrain, Maggie M. (Author)
Simpson, Elizabeth (Author)
Dyson, Julian (Author)
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