title: The role of production frequency in the sharing of simian immunodeficiency virus-specific CD8+ TCRs between macaques.
abstract: 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 beta-chains in the CD8(+) T cell responses to two influenza epitopes in mice. Analysis of these TCRbeta repertoires suggests that, even with unbiased V(D)J recombination mechanisms, some TCRbetas can be produced more frequently than others, by a process of convergent recombination. The TCRbeta production frequency was shown to be a good predictor of the observed sharing of epitope-specific TCRbetas between mice. However, this study was limited to immune responses in an inbred population. In this study, we investigated TCRbeta 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 approximately 6000 TCRbetas sampled from 20 macaques. We observed a spectrum in the number of macaques sharing epitope-specific TCRbetas in this outbred population. This spectrum of TCRbeta 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 TCRbeta 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 TCRbeta sharing.
authors.affiliation: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Kensington, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Venturi
authors.forename: Hui Yee
authors.initials: HY
authors.lastname: Chin
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D016415:Sequence Alignment; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta