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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cancer+Immunol+Res 2015 ; 3 (3): 228-35 Nephropedia Template TP
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Peptide/MHC tetramer-based sorting of CD8+ T cells to a leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire #MMPMID25576336
Cancer Immunol Res 2015[Mar]; 3 (3): 228-35 PMID25576336show ga
Testing of T cell-based cancer therapeutics often involves measuring cancer antigen-specific T-cell populations with the assumption that they arise from in vivo clonal expansion. This analysis, using peptide/MHC tetramers, is often ambiguous.From a leukemia cell line, we identified a CDK4-derived peptide epitope, UNC-CDK4-1 (ALTPVVVTL) that bound HLA-A*02:01 with high affinity and could induce CD8+ T-cell responses in vitro. We identified UNC-CDK4-1/HLA-A*02:01 tetramer+ populations in 3 of 6 patients with acute myeloid leukemia who had undergone allogeneic stem cell transplant (SCT).Using tetramer-based, single-cell sorting and T-cell receptor ? (TCR?) sequencing we identified recurrent UNC-CDK4-1 tetramer-associated TCR? clonotypes in a patient with a UNC-CDK4-1 tetramer+ population, suggesting in vivo T-cell expansion to UNC-CDK4-1. In parallel, we measured the patient's TCR? repertoire and found it to be highly restricted / oligoclonal. The UNC-CDK4-1 tetramer-associated TCR? clonotypes represented >17% of the entire TCR? repertoire ? far in excess of the UNC-CDK4-1 tetramer+ frequency, indicating that the recurrent TCR? clonotypes identified from UNC-CDK-4-1 tetramer+ cells were likely a consequence of the extremely constrained T-cell repertoire in the patient and not in vivo UNC-CDK4-1-driven clonal T-cell expansion.Mapping recurrent TCR? clonotype sequences onto TCR? repertoires can help confirm or refute antigen-specific T-cell expansion in vivo.