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Medientyp:
E-Artikel
Titel:
Abundant cytomegalovirus (CMV) reactive clonotypes in the CD8+ T cell receptor alpha repertoire following allogeneic transplantation
Beteiligte:
Link, C S;
Eugster, A;
Heidenreich, F;
Rücker-Braun, E;
Schmiedgen, M;
Oelschlägel, U;
Kühn, D;
Dietz, S;
Fuchs, Y;
Dahl, A;
Domingues, A M J;
Klesse, C;
Schmitz, M;
Ehninger, G;
Bornhäuser, M;
Schetelig, J;
Bonifacio, E
Erschienen:
Oxford University Press (OUP), 2016
Erschienen in:Clinical and Experimental Immunology
Sprache:
Englisch
DOI:
10.1111/cei.12770
ISSN:
0009-9104;
1365-2249
Entstehung:
Anmerkungen:
Beschreibung:
<jats:title>Summary</jats:title>
<jats:p>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-α repertoire and its clinical relevance in patients following stem cell transplantation. Using next-generation sequencing we examined the TCR-α repertoire of CD8+ T cells and CMV-specific CD8+ T cells in four patients. Additionally, we performed single-cell TCR-αβ sequencing of CMV-specific CD8+ T cells. The TCR-α 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-α 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-α 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.</jats:p>