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10.1158/2326-6066.CIR-14-0001

http://scihub22266oqcxt.onion/10.1158/2326-6066.CIR-14-0001
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C4351150!4351150 !25576336
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suck abstract from ncbi


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pmid25576336
      Cancer+Immunol+Res 2015 ; 3 (3 ): 228-35
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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
  • Hunsucker SA ; McGary CS ; Vincent BG ; Enyenihi AA ; Waugh JP ; McKinnon KP ; Bixby LM ; Ropp PA ; Coghill JM ; Wood WA ; Gabriel DA ; Sarantopoulos S ; Shea TC ; Serody JS ; Alatrash G ; Rodriguez-Cruz T ; Lizée G ; Buntzman AS ; Frelinger JA ; Glish GL ; Armistead PM
  • Cancer Immunol Res 2015[Mar]; 3 (3 ): 228-35 PMID25576336 show 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 transplantation. 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.
  • |Antigens, Neoplasm/*immunology [MESH]
  • |CD8-Positive T-Lymphocytes/*immunology [MESH]
  • |Epitopes, T-Lymphocyte/*immunology [MESH]
  • |Female [MESH]
  • |HLA-A2 Antigen/immunology [MESH]
  • |Humans [MESH]
  • |Leukemia/immunology [MESH]
  • |Male [MESH]
  • |Middle Aged [MESH]
  • |Peptides/immunology [MESH]
  • |Receptors, Antigen, T-Cell, alpha-beta/*immunology [MESH]
  • |T-Lymphocyte Subsets/*immunology [MESH]


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