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Clonotype Tracking of TCR Repertoires during Chronic Virus Infections
- Source :
-
Virology . Dec2002, Vol. 304 Issue 2, p474. 11p. - Publication Year :
- 2002
-
Abstract
- Human viral infections such as HIV and EBV typically evoke a strong and diverse CD8+ T cell response. Relatively little is known about the extent to which TCR repertoire evolution occurs during viral infection or how repertoire evolution affects the efficacy of the CD8+ T cell response. In this study we describe a general approach for tracking TCR repertoire evolution during viral infection. IFNγ surface capture and MHC class I tetramer staining were independently used to isolate EBV-specific CD8+ T cells from peripheral blood. Anchored RT-PCR and clonotype TCR repertoire analysis were performed immediately after isolating the cells. We find that the TCR repertoires of the IFNγ-secreting and MHC class I tetramer staining populations were similar. In one subject a detailed analysis of the TCR repertoire during the first year of EBV infection was performed and over 600 TCR sequences targeting an EBV-immunodominant epitope were analyzed. Although some repertoire evolution occurred during the year, in general, the degree of repertoire drift was small. TCR repertoire analysis for an HIV-immunodominant epitope revealed a highly conserved amino acid motif in the Dβ region of TCR that recognizes the epitope and suggested that T cell precursor frequency influences which epitopes are targeted early in HIV infection. This methodology, which allows one to sort antigen-specific T cells based on different functional assays and to obtain a snapshot of their TCR repertoire with relative ease, should lead to a richer understanding of the rules underlying antigen recognition and T cell evolution during viral infection. [Copyright &y& Elsevier]
- Subjects :
- *VIRUS diseases
*BIOLOGICAL evolution
Subjects
Details
- Language :
- English
- ISSN :
- 00426822
- Volume :
- 304
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 8721460
- Full Text :
- https://doi.org/10.1006/viro.2002.1743