Journal article

IMGT/HighV QUEST paradigm for T cell receptor IMGT clonotype diversity and next generation repertoire immunoprofiling

Shuo Li, Marie-Paule Lefranc, John J Miles, Eltaf Alamyar, Veronique Giudicelli, Patrice Duroux, J Douglas Freeman, Vincent DA Corbin, Jean-Pierre Scheerlinck, Michael A Frohman, Paul U Cameron, Magdalena Plebanski, Bruce Loveland, Scott R Burrows, Anthony T Papenfuss, Eric J Gowans



T cell repertoire diversity and clonotype follow-up in vaccination, cancer, infectious and immune diseases represent a major challenge owing to the enormous complexity of the data generated. Here we describe a next generation methodology, which combines 5'RACE PCR, 454 sequencing and, for analysis, IMGT, the international ImMunoGeneTics information system (IMGT), IMGT/HighV-QUEST web portal and IMGT-ONTOLOGY concepts. The approach is validated in a human case study of T cell receptor beta (TRB) repertoire, by chronologically tracking the effects of influenza vaccination on conventional and regulatory T cell subpopulations. The IMGT/HighV-QUEST paradigm defines standards for genotype/haplotyp..

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Funding Acknowledgements

We thank A. Skarshewski from AGRF for help with raw data processing before IMGT/HighV-QUEST analysis; M. Tinning from AGRF for helpful advice on experimental design; A. Lucas from the Institute for Immunology and Infectious Diseases, Western Australia, for conducting HLA typing; the AMREP Flow Cytometry Facility for cell sorting; S. Turner from the Department of Microbiology and Immunology, The University of Melbourne, for helpful discussions and reading of the manuscript; V. Venturi from Complex Systems Biology Group, University of New South Wales, for helpful discussions and advice on data annotation. This work was supported by grant number 543143 from the National Health and Medical Research Council (NHMRC) Australia and a private donation to the Burnet Institute. J.J.M. is a NHMRC Career Development Fellow supported by a Wales Office of Research and Development (WORD) Research Funding Scheme, S. R. B. and E.J.G. are NHMRC Senior Research Fellows. We gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program. IMGT is funded by the Ministere de l'Enseignement Superieur et de la Recherche (MESR), Centre National de la Recherche Scientifique (CNRS) and Universite Montpellier 2, France. IMGT/HighV-QUEST was granted access to the HPC resources of CINES under the allocation 2010-2013-036029 made by GENCI (Grand Equipement National de Calcul Intensif).