Peptide/MHC tetramer-based sorting of CD8⺠T cells to a leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire.
Cancer Immunol Res
; 3(3): 228-35, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25576336
ABSTRACT
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*0201 with high affinity and could induce CD8⺠T-cell responses in vitro. We identified UNC-CDK4-1/HLA-A*0201 tetramer⺠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 ß (TCRß) sequencing, we identified recurrent UNC-CDK4-1 tetramer-associated TCRß clonotypes in a patient with a UNC-CDK4-1 tetramer⺠population, suggesting in vivo T-cell expansion to UNC-CDK4-1. In parallel, we measured the patient's TCRß repertoire and found it to be highly restricted/oligoclonal. The UNC-CDK4-1 tetramer-associated TCRß clonotypes represented >17% of the entire TCRß repertoire-far in excess of the UNC-CDK4-1 tetramer⺠frequency-indicating that the recurrent TCRß clonotypes identified from UNC-CDK-4-1 tetramer⺠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 TCRß clonotype sequences onto TCRß repertoires can help confirm or refute antigen-specific T-cell expansion in vivo.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
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Receptores de Antígenos de Linfócitos T alfa-beta
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Antígenos de Neoplasias
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cancer Immunol Res
Ano de publicação:
2015
Tipo de documento:
Article