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Figure 1. Schematic representation of antigen-driven T-cell activation. An antigen-presenting cell, in this case a dendritic cell, interacts with an antigen indicated here as 'pathogen'. The antigen is appropriately modified by the dendritic cell and presented to a naive T cell via MHC class II. T-cell interaction with the complex antigen/MHC class II is mediated by a specific TCR, which is unique for that antigen and characterizes a T-cell clonotype. Activation of the T cell then requires a co-stimulation of the CD28 receptor. Once activated, the T cell may follow different pathways: a Th1 response is a proinflammatory response, characterized by production, among others, of large amounts of IFN-γ, which may then activate macrophages. Th2 response is, in contrast, characterized by the production of anti-inflammatory cytokines, such as IL-10 and tends to dampen the reaction. Differentiation into a Th1 or Th2 lineage depends on many factors, including micro-environmental cytokine production. For example, simultaneous stimulation of the activated T lymphocytes with IL-12 produced by the dendritic cell will predominantly shift toward a Th1 response. PAMP: Pathogen-associated molecular pattern; PRR: Pattern recognition receptor; TCR: T-cell receptor.
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Figure 2. Analysis of the T-cell repertoire within unstable plaques. (A) T cells recognize antigens using a specific structure, the T cell receptor (TCR) (black arrows). The TCR is a heterodimer expressed on the cell membrane and belongs to the Immunoglobulin superfamily; it is formed by αβ or γδ chains. Over 95% of circulating T cells express αβ TCR. Genes coding for TCR proteins undergo gene rearrangements as for Ig genes: V-D-J and C gene segments are involved in this process. Each rearrangement is unique and defines a cell clonotype. The TCR chains are organized in CDR1, CDR2 and CDR3 regions, the latter being critical for specific antigen recognition. Each T cell rearranges productively only one β chain due to an allelic exclusion phenomenon, while different αchains may be rearranged. To date, 25 Vβ families and 35 Vαfamilies have been described. The T-cell repertoire can be investigated using a specific PCR-based technique, commonly referred to as spectratyping, which allows us to amplify the different CDR3 regions of the TCR β families. After RNA and cDNA preparation, the different samples are amplified using primers for the...