Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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TCR affinity-dependent functional inhibition via PD-1 and SHP-1 phosphatase

ABSTRACT: To investigate gene expression changes associated with stimulation of TCRs of different affinity, primary CD8 T cells were transduced with sequence optimized TCRs of various affinities and stimulated for 6h. Gene expression was measured at baseline (0h) and after 6h after stimulation with low dose NY-ESO-1 multimer

ORGANISM(S): Homo sapiens

SUBMITTER: Lukas Baitsch 

PROVIDER: E-GEOD-42922 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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SHP-1 phosphatase activity counteracts increased T cell receptor affinity.

Hebeisen Michael M   Baitsch Lukas L   Presotto Danilo D   Baumgaertner Petra P   Romero Pedro P   Michielin Olivier O   Speiser Daniel E DE   Rufer Nathalie N  

The Journal of clinical investigation 20130208 3

Anti-self/tumor T cell function can be improved by increasing TCR-peptide MHC (pMHC) affinity within physiological limits, but paradoxically further increases (K(d) < 1 μM) lead to drastic functional declines. Using human CD8(+) T cells engineered with TCRs of incremental affinity for the tumor antigen HLA-A2/NY-ESO-1, we investigated the molecular mechanisms underlying this high-affinity-associated loss of function. As compared with cells expressing TCR affinities generating optimal function (K  ...[more]

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