Persistent viral infection in humans can drive high frequency low-affinity T-cell expansions.
Immunology
; 131(4): 537-48, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20722762
ABSTRACT
CD8 T cells that recognize cytomegalovirus (CMV) -encoded peptides can be readily detected by staining with human leucocyte antigen (HLA) -peptide tetramers. These cells are invariably highly differentiated effector memory cells with high avidity T-cell receptors (TCR). In this report we demonstrate an HLA-A*0201 restricted CMV-specific CD8 T-cell response (designated YVL) that represents several percent of the CD8 T-cell subset, yet fails to bind tetrameric major histocompatibility complex (MHC) ligands. However, these tetramer-negative cells are both phenotypically and functionally similar to other CMV-specific CD8 T cells. YVL peptide-specific CD8 T-cell clones were generated and found to be of high avidity in both cytotoxicity and interferon-γ (IFN-γ) assays, and comparable with other CMV peptide-specific CD8 T-cell clones. However, under conditions of CD8 blockade, the response was almost nullified even at very high ligand concentrations. This was also the case in IFN-γ experiments using peripheral blood mononuclear cells stimulated with peptide ex vivo. In contrast, all other CMV specificities (tetramer-positive) displayed minimal or only partial CD8 dependence. This suggests that YVL-specific responses depict a low-affinity TCR-MHC-peptide interaction, that is compensated by substantial CD8 involvement for functional purposes, yet cannot engage multivalent soluble ligands for ex vivo analysis. It is interesting that such a phenomenon is apparent in the face of a persistent virus infection such as CMV, where the responding cells represent an immunodominant response in that individual and may present a highly differentiated effector phenotype.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Antígenos HLA-A
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Subpopulações de Linfócitos T
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Infecções por Citomegalovirus
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Linfócitos T CD8-Positivos
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Citomegalovirus
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article