Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8(+) T cell receptor alpha repertoire following allogeneic transplantation

作者：Link C S^*; Eugster A; Heidenreich F; Ruecker Braun E; Schmiedgen M; Oelschlaegel U; Kuehn D; Dietz S; Fuchs Y; Dahl A; Domingues A M J; Klesse C; Schmitz M; Ehninger G; Bornhaeuser M; Schetelig J; Bonifacio E

来源：Clinical and Experimental Immunology, 2016, 184(3): 389-402.

DOI：10.1111/cei.12770

• allogeneic transplantation
• CMV
• next-generation sequencing
• T cell receptor alpha
• T cell receptor repertoire

Allogeneic stem cell transplantation is potentially curative, but associated with post-transplantation complications, including cytomegalovirus (CMV) infections. An effective immune response requires T cells recognizing CMV epitopes via their T cell receptors (TCRs). Little is known about the TCR repertoire, in particular the TCR-alpha repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-alpha repertoire of CD8(+) T cells and CMV-specific CD8(+) T cells in four patients. Additionally, we performed single-cell TCR-alpha beta sequencing of CMV-specific CD8(+) T cells. The TCR-alpha composition of human leucocyte antigen (HLA)-A*0201 CMVpp65- and CMVIE-specific T cells was oligoclonal and defined by few dominant clonotypes. Frequencies of single clonotypes reached up to 11% of all CD8(+) T cells and half of the total CD8(+) T cell repertoire was dominated by few CMV-reactive clonotypes. Some TCR-alpha clonotypes were shared between patients. Gene expression of the circulating CMV-specific CD8(+) T cells was consistent with chronically activated effector memory T cells. The CD8(+) T cell response to CMV reactivation resulted in an expansion of a few TCR-alpha clonotypes to dominate the CD8(+) repertoires. These results warrant further larger studies to define the ability of oligoclonally expanded T cell clones to achieve an effective anti-viral T cell response in this setting.

• 出版日期2016-6