TY - JOUR
T1 - High-throughput sequencing reveals an altered T cell repertoire in X-linked agammaglobulinemia
AU - Ramesh, Manish
AU - Simchoni, Noa
AU - Hamm, David
AU - Cunningham-Rundles, Charlotte
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health ( AI 101093 , AI-086037 , AI-48693 , T32-GM007280 ), The Jeffrey Modell Foundation , and the David S Gottesman Immunology Chair .
Funding Information:
We would like to thank Lin Radigan for her technical help without which this study would not have been possible. We would like to thank Harlan Robins and Adaptive Biotech Inc. for their generous support for sequencing and informatics. We would like to acknowledge the invaluable assistance of Lisa J. Edelmann PhD and Mount Sinai Genetic testing Laboratory who provided the control DNA used in this work. This work was supported in part through the computational resources and staff expertise provided by the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - To examine the T cell receptor structure in the absence of B cells, the TCR β CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non-productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vβ gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA.
AB - To examine the T cell receptor structure in the absence of B cells, the TCR β CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non-productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vβ gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA.
KW - Amino acid sequence
KW - High throughput sequencing
KW - Junctional diversity
KW - T cell receptor
KW - XLA
UR - http://www.scopus.com/inward/record.url?scp=84942575118&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942575118&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2015.09.002
DO - 10.1016/j.clim.2015.09.002
M3 - Article
C2 - 26360253
AN - SCOPUS:84942575118
SN - 1521-6616
VL - 161
SP - 190
EP - 196
JO - Clinical Immunology
JF - Clinical Immunology
IS - 2
ER -