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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Cancer+Immunol+Res
2015 ; 3
(3
): 228-35
Nephropedia Template TP
gab.com Text
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English Wikipedia
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.