Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection

Schober, Kilian; Voit, Florian; Grassmann, Simon; Müller, Thomas R.; Eggert, Joel; Jarosch, Sebastian; Weißbrich, Bianca; Hoffmann, Patrick; Borkner, Lisa; Nio, Enzo; Fanchi, Lorenzo; Clouser, Christopher R.; Radhakrishnan, Aditya; Mihatsch, Lorenz; Lückemeier, Philipp; Leube, Justin; Dössinger, Georg; Klein, Ludger; Neuenhahn, Michael; Oduro, Jennifer D.; Cicin-Sain, Luka; Buchholz, Veit R. und Busch, Dirk H. (2020): Reverse TCR repertoire evolution toward dominant low-affinity clones during chronic CMV infection. In: Nature Immunology, Bd. 21, Nr. 4: S. 434-441

Abstract

Adaptive evolution is a key feature of T cell immunity. During acute immune responses, T cells harboring high-affinity T cell antigen receptors (TCRs) are preferentially expanded, but whether affinity maturation by clonal selection continues through the course of chronic infections remains unresolved. Here we investigated the evolution of the TCR repertoire and its affinity during the course of infection with cytomegalovirus, which elicits large T cell populations in humans and mice. Using single-cell and bulk TCR sequencing and structural affinity analyses of cytomegalovirus-specific T cells, and through the generation and in vivo monitoring of defined TCR repertoires, we found that the immunodominance of high-affinity T cell clones declined during the chronic infection phase, likely due to cellular senescence. These data showed that under conditions of chronic antigen exposure, low-affinity TCRs preferentially expanded within the TCR repertoire, with implications for immunotherapeutic strategies. Busch and colleagues use single-cell and bulk TCR sequencing and structural affinity analyses of CMV-specific T cells to show that the immunodominance of high-affinity T cell clones declines during chronic infection with CMV, likely due to cellular senescence.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1529-2908
• Sprache: Englisch