deep sequencing of antiviral t-cell responses to hcmv and ebv in humans reveals a stable repertoire that is maintained for many years深度测序的抗病毒t细胞反应和ebv血巨细胞病毒在人类揭示了一个稳定的曲目,是多年来维护的.pdf

Deep Sequencing of Antiviral T-Cell Responses to HCMV and EBV in Humans Reveals a Stable Repertoire That Is Maintained for Many Years P. L. Klarenbeek1,2,3., E. B. M. Remmerswaal3,4., I. J. M. ten Berge3,4, M. E. Doorenspleet1,2,3, B. D. C. van 5 1,2,3 3 6 5 4 1 Schaik , R. E. E. Esveldt , S. D. Koch , A. ten Brinke , A. H. C. van Kampen , F. J. Bemelman , P. P. Tak , 2 1 3,6 F. Baas , N. de Vries , R. A. W. van Lier * 1 Department of Clinical Immunology Rheumatology, Academic Medical Center, Amsterdam, the Netherlands, 2 Department of Genome Analysis, Academic Medical Center, Amsterdam, the Netherlands, 3 Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands, 4 Renal Transplant Unit, Academic Medical Center, Amsterdam, the Netherlands, 5 Bioinformatics Laboratory, Academic Medical Center, Amsterdam, the Netherlands, 6 Sanquin Research at CLB and Landsteiner Laboratory, Amsterdam, the Netherlands Abstract CD8+ T-cell responses against latent viruses can cover considerable portions of the CD8+ T-cell compartment for many decades, yet their initiation and maintenance remains poorly characterized in humans. A key question is whether the clonal repertoire that is raised during the initial antiviral response can be maintained over these long periods. To investigate this we combined next-generation sequencing of the T-cell receptor repertoire with tetramer-sorting to identify, quantify and longitudinally follow virus-specific clones within the CD8+ T-cell compartment. Using this approach we studied primary infections of human cytomegalovirus (hCMV) and Epstein Barr virus (EB