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* Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;
Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892;
Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, United Kingdom; and
Centre for Immunology, St. Vincent’s Hospital and National Centre in HIV Epidemiology and Clinical Research (University of New South Wales), Sydney, Australia
The CD8+ TCR repertoires specific for many immunogenic epitopes of CMV and EBV are dominated by a few TCR clonotypes and involve public TCRs that are shared between many MHC-matched individuals. In previous studies, we demonstrated that the observed sharing of epitope-specific TCRβ chains between individuals is strongly associated with TCRβ production frequency, and that a process of convergent recombination facilitates the more efficient production of some TCRβ sequences. In this study, we analyzed a total of 2836 TCRβ sequences from 23 CMV-infected and 10 EBV-infected individuals to investigate the factors that influence the sharing of TCRβ sequences in the CD8+ T cell responses to two immunodominant HLA-A*0201-restricted epitopes from these viruses. The most shared TCRβ amino acid sequences were found to have two features that indicate efficient TCRβ production, as follows: 1) they required fewer nucleotide additions, and 2) they were encoded by a greater variety of nucleotide sequences. We used simulations of random V(D)J recombination to demonstrate that the in silico TCRβ production frequency was predictive of the extent to which both TCRβ nucleotide and amino acid sequences were shared in vivo. These results suggest that TCRβ production frequency plays an important role in the interindividual sharing of TCRβ sequences within CD8+ T cell responses specific for CMV and EBV.
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 James S. McDonnell Foundation 21st Century Research Award/Studying Complex Systems, the Australian Research Council, the National Health and Medical Research Council, and the National Institutes of Health. M.P.D. is a Sylvia and Charles Viertel Senior Medical Research Fellow, and D.A.P. is a Medical Research Council (U.K.) Senior Clinical Fellow.
2 Address correspondence and reprint requests to Dr. Miles P. Davenport, Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington NSW 2052, Australia. E-mail address: m.davenport{at}unsw.edu.au or Dr. David A. Price, Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff CF14 4XN, U.K.; E-mail address: priced6{at}cardiff.ac.uk
3 The online version of this article contains supplemental material.
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