|
|
||||||||
,

* Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia;
Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, United Kingdom; and
Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD 20892
In some epitope-specific responses, T cells bearing identical TCRs occur in many MHC-matched individuals. The sharing of public TCRs is unexpected, given the enormous potential diversity of the TCR repertoire. We have previously studied the sharing of TCR β-chains in the CD8+ T cell responses to two influenza epitopes in mice. Analysis of these TCRβ repertoires suggests that, even with unbiased V(D)J recombination mechanisms, some TCRβs can be produced more frequently than others, by a process of convergent recombination. The TCRβ production frequency was shown to be a good predictor of the observed sharing of epitope-specific TCRβs between mice. However, this study was limited to immune responses in an inbred population. In this study, we investigated TCRβ sharing in CD8+ T cell responses specific for the immunodominant Mamu-A*01-restricted Tat-SL8/TL8 and Gag-CM9 epitopes of SIV in rhesus macaques. Multiple data sets were used, comprising a total of
6000 TCRβs sampled from 20 macaques. We observed a spectrum in the number of macaques sharing epitope-specific TCRβs in this outbred population. This spectrum of TCRβ sharing was negatively correlated with the minimum number of nucleotide additions required to produce the sequences and strongly positively correlated with the number of observed nucleotide sequences encoding the amino acid sequences. We also found that TCRβ sharing was correlated with the number of times, and the variety of different ways, the sequences were produced in silico via random gene recombination. Thus, convergent recombination is a major determinant of the extent of TCRβ sharing.
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, 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 (United Kingdom) 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
This article has been cited by other articles:
![]() |
D. A. Price, T. E. Asher, N. A. Wilson, M. C. Nason, J. M. Brenchley, I. S. Metzler, V. Venturi, E. Gostick, P. K. Chattopadhyay, M. Roederer, et al. Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection J. Exp. Med., April 13, 2009; 206(4): 923 - 936. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Venturi, H. Y. Chin, T. E. Asher, K. Ladell, P. Scheinberg, E. Bornstein, D. van Bockel, A. D. Kelleher, D. C. Douek, D. A. Price, et al. TCR {beta}-Chain Sharing in Human CD8+ T Cell Responses to Cytomegalovirus and EBV J. Immunol., December 1, 2008; 181(11): 7853 - 7862. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |