Journal
FRONTIERS IN IMMUNOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.01290
Keywords
CD8 T cells; Toxoplasma gondii; neurological infection and inflammation; T cell receptor-major histocompatibility complex interaction; ROP7
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Funding
- NIH Tetramer Core Facility [HHSN272201300006C]
- Francis Crick Institute from Cancer Research UK [FC001076]
- UK Medical Research Council [FC001076]
- Wellcome Trust [FC001076]
- Wellcome Trust Career Development Fellowship [091664/B/10/Z]
- MRC [MC_UP_1202/12] Funding Source: UKRI
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T cell receptor-major histocompatibility complex (TCR-MHC) affinities span a wide range in a polyclonal T cell response, yet it is undefined how affinity shapes long-term properties of CD8 T cells during chronic infection with persistent antigen. Here, we investigate how the affinity of the TCR-MHC interaction shapes the phenotype of memory CD8 T cells in the chronically Toxoplasma gondii-infected brain. We employed CD8 T cells from three lines of transnuclear (TN) mice that harbor in their endogenous loci different T cell receptors specific for the same Toxoplasma antigenic epitope ROP7. The three TN CD8 T cell clones span a wide range of affinities to MHCI-ROP7. These three CD8 T cell clones have a distinct and fixed hierarchy in terms of effector function in response to the antigen measured as proliferation capacity, trafficking, T cell maintenance, and memory formation. In particular, the T cell clone of lowest affinity does not home to the brain. The two higher affinity T cell clones show differences in establishing resident-like memory populations (CD103(+)) in the brain with the higher affinity clone persisting longer in the host during chronic infection. Transcriptional profiling of naive and activated ROP7-specific CD8 T cells revealed that Klf2 encoding a transcription factor that is known to be a negative marker for T cell trafficking is upregulated in the activated lowest affinity ROP7 clone. Our data thus suggest that TCR-MHC affinity dictates memory CD8 T cell fate at the site of infection.
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