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Public T Cell Receptor β-Chains Are Not Advantaged during Positive Selection¹

Anna L. Furmanski^2,3,*, Cristina Ferreira^*, Istvan Bartok^*, Sofia Dimakou^*, Jason Rice, Freda K. Stevenson, Maggie M. Millrain^*, Elizabeth Simpson^* and Julian Dyson^3,*

^* Department of Immunology, Hammersmith Hospital, Imperial College London, London, United Kingdom; and Molecular Immunology Group, Tenovus Laboratory, University of Southampton, Southampton, United Kingdom

Studies of human and murine T cells have shown that public TCR β-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^bSmcy share an invariant Vβ8.2-Jβ2.3 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 β-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 Vβ8.2-Jβ2.3 CDR3 loops from naive T cell repertoires of multiple mice. Public TCR β-chain sequences were identified across different repertoires and MHC haplotypes. To determine whether such public β-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 β-chains were positively selected with similar efficiency regardless of CDR3 loop sequence. Therefore, the establishment and maintenance of public β-chains in the periphery is predominantly controlled by post-thymic events through modification of the primary, thymus-derived TCR repertoire.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Medical Research Council.

² Current address: Immunobiology Unit, Institute of Child Health, University College London, London, U.K.

³ Address correspondence and reprint requests to Prof. Anna L. Furmanski or Dr. Julian Dyson, Imperial College London, Commonwealth Building, Hammersmith Hospital, London, W12 0NN, U.K. E-mail addresses: a.furmanski{at}ich.ucl.ac.uk and peter.dyson{at}imperial.ac.uk

⁴ Abbreviations used in this paper: B6, C57BL/6; APP, APPAGAETL; BM, bone marrow; DN, double negative; DP double positive; GGG, GGGLGGRAETL; HSC, hemopoietic stem cell; SP, single positive; SP4, CD4 SP thymocyte population; SP8, CD8 SP thymocyte population; SPF, specific pathogen free.