Peptide/MHC tetramer-based sorting of CD8 T cells to a Leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire

Sally A. Hunsucker, Colleen S. McGary, Benjamin G. Vincent, Atim A. Enyenihi, Jennifer P. Waugh, Karen P. McKinnon, Lisa M. Bixby, Patricia A. Ropp, James M. Coghill, William A. Wood, Don A. Gabriel, Stefanie Sarantopoulos, Thomas C. Shea, Jonathan S. Serody, Gheath Alatrash, Tania Rodriguez-Cruz, Gregory Lizee, Adam S. Buntzman, Jeffrey A Frelinger, Gary L. GlishPaul M. Armistead

Research output: Contribution to journalArticle

9 Citations (Scopus)

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-A02:01 with high affinity and could induce CD8+ T-cell responses in vitro. We identified UNCCDK4-1/HLA-A02:01 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 b (TCRb) sequencing, we identified recurrent UNC-CDK4-1 tetramer-associated TCRb clonotypes in a patient with aUNC-CDK4-1 tetramer+ population, suggestingin vivo T-cell expansion to UNC-CDK4-1. In parallel, we measured the patient's TCRb repertoire and found it to be highly restricted/oligoclonal. The UNC-CDK4-1 tetramer-associated TCRb clonotypes represented >17% of the entire TCRb repertoire - far in excess of the UNCCDK4-1 tetramer+ frequency - indicating that the recurrent TCRb 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 TCRb clonotype sequences onto TCRb repertoires can help confirm or refute antigen-specific T-cell expansion.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalCancer immunology research
Volume3
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

T-Cell Antigen Receptor
Leukemia
T-Lymphocytes
Antigens
Peptides
varespladib methyl
Population
Stem Cell Transplantation
Acute Myeloid Leukemia
Epitopes
Neoplasms
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Immunology

Cite this

Peptide/MHC tetramer-based sorting of CD8 T cells to a Leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire. / Hunsucker, Sally A.; McGary, Colleen S.; Vincent, Benjamin G.; Enyenihi, Atim A.; Waugh, Jennifer P.; McKinnon, Karen P.; Bixby, Lisa M.; Ropp, Patricia A.; Coghill, James M.; Wood, William A.; Gabriel, Don A.; Sarantopoulos, Stefanie; Shea, Thomas C.; Serody, Jonathan S.; Alatrash, Gheath; Rodriguez-Cruz, Tania; Lizee, Gregory; Buntzman, Adam S.; Frelinger, Jeffrey A; Glish, Gary L.; Armistead, Paul M.

In: Cancer immunology research, Vol. 3, No. 3, 01.03.2015, p. 228-235.

Research output: Contribution to journalArticle

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, Lizee, G, Buntzman, AS, Frelinger, JA, Glish, GL & Armistead, PM 2015, 'Peptide/MHC tetramer-based sorting of CD8 T cells to a Leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire', Cancer immunology research, vol. 3, no. 3, pp. 228-235. https://doi.org/10.1158/2326-6066.CIR-14-0001
Hunsucker, Sally A. ; McGary, Colleen S. ; Vincent, Benjamin G. ; Enyenihi, Atim A. ; Waugh, Jennifer P. ; McKinnon, Karen P. ; Bixby, Lisa M. ; Ropp, Patricia A. ; Coghill, James M. ; Wood, William A. ; Gabriel, Don A. ; Sarantopoulos, Stefanie ; Shea, Thomas C. ; Serody, Jonathan S. ; Alatrash, Gheath ; Rodriguez-Cruz, Tania ; Lizee, Gregory ; Buntzman, Adam S. ; Frelinger, Jeffrey A ; Glish, Gary L. ; Armistead, Paul M. / Peptide/MHC tetramer-based sorting of CD8 T cells to a Leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire. In: Cancer immunology research. 2015 ; Vol. 3, No. 3. pp. 228-235.
@article{f35985a922074adaa970516947aed835,
title = "Peptide/MHC tetramer-based sorting of CD8 T cells to a Leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire",
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∗02:01 with high affinity and could induce CD8+ T-cell responses in vitro. We identified UNCCDK4-1/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 b (TCRb) sequencing, we identified recurrent UNC-CDK4-1 tetramer-associated TCRb clonotypes in a patient with aUNC-CDK4-1 tetramer+ population, suggestingin vivo T-cell expansion to UNC-CDK4-1. In parallel, we measured the patient's TCRb repertoire and found it to be highly restricted/oligoclonal. The UNC-CDK4-1 tetramer-associated TCRb clonotypes represented >17{\%} of the entire TCRb repertoire - far in excess of the UNCCDK4-1 tetramer+ frequency - indicating that the recurrent TCRb 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 TCRb clonotype sequences onto TCRb repertoires can help confirm or refute antigen-specific T-cell expansion.",
author = "Hunsucker, {Sally A.} and McGary, {Colleen S.} and Vincent, {Benjamin G.} and Enyenihi, {Atim A.} and Waugh, {Jennifer P.} and McKinnon, {Karen P.} and Bixby, {Lisa M.} and Ropp, {Patricia A.} and Coghill, {James M.} and Wood, {William A.} and Gabriel, {Don A.} and Stefanie Sarantopoulos and Shea, {Thomas C.} and Serody, {Jonathan S.} and Gheath Alatrash and Tania Rodriguez-Cruz and Gregory Lizee and Buntzman, {Adam S.} and Frelinger, {Jeffrey A} and Glish, {Gary L.} and Armistead, {Paul M.}",
year = "2015",
month = "3",
day = "1",
doi = "10.1158/2326-6066.CIR-14-0001",
language = "English (US)",
volume = "3",
pages = "228--235",
journal = "Cancer immunology research",
issn = "2326-6066",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Peptide/MHC tetramer-based sorting of CD8 T cells to a Leukemia antigen yields clonotypes drawn nonspecifically from an underlying restricted repertoire

AU - Hunsucker, Sally A.

AU - McGary, Colleen S.

AU - Vincent, Benjamin G.

AU - Enyenihi, Atim A.

AU - Waugh, Jennifer P.

AU - McKinnon, Karen P.

AU - Bixby, Lisa M.

AU - Ropp, Patricia A.

AU - Coghill, James M.

AU - Wood, William A.

AU - Gabriel, Don A.

AU - Sarantopoulos, Stefanie

AU - Shea, Thomas C.

AU - Serody, Jonathan S.

AU - Alatrash, Gheath

AU - Rodriguez-Cruz, Tania

AU - Lizee, Gregory

AU - Buntzman, Adam S.

AU - Frelinger, Jeffrey A

AU - Glish, Gary L.

AU - Armistead, Paul M.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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 UNCCDK4-1/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 b (TCRb) sequencing, we identified recurrent UNC-CDK4-1 tetramer-associated TCRb clonotypes in a patient with aUNC-CDK4-1 tetramer+ population, suggestingin vivo T-cell expansion to UNC-CDK4-1. In parallel, we measured the patient's TCRb repertoire and found it to be highly restricted/oligoclonal. The UNC-CDK4-1 tetramer-associated TCRb clonotypes represented >17% of the entire TCRb repertoire - far in excess of the UNCCDK4-1 tetramer+ frequency - indicating that the recurrent TCRb 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 TCRb clonotype sequences onto TCRb repertoires can help confirm or refute antigen-specific T-cell expansion.

AB - 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 UNCCDK4-1/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 b (TCRb) sequencing, we identified recurrent UNC-CDK4-1 tetramer-associated TCRb clonotypes in a patient with aUNC-CDK4-1 tetramer+ population, suggestingin vivo T-cell expansion to UNC-CDK4-1. In parallel, we measured the patient's TCRb repertoire and found it to be highly restricted/oligoclonal. The UNC-CDK4-1 tetramer-associated TCRb clonotypes represented >17% of the entire TCRb repertoire - far in excess of the UNCCDK4-1 tetramer+ frequency - indicating that the recurrent TCRb 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 TCRb clonotype sequences onto TCRb repertoires can help confirm or refute antigen-specific T-cell expansion.

UR - http://www.scopus.com/inward/record.url?scp=84961922850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961922850&partnerID=8YFLogxK

U2 - 10.1158/2326-6066.CIR-14-0001

DO - 10.1158/2326-6066.CIR-14-0001

M3 - Article

C2 - 25576336

AN - SCOPUS:84961922850

VL - 3

SP - 228

EP - 235

JO - Cancer immunology research

JF - Cancer immunology research

SN - 2326-6066

IS - 3

ER -