Hepatitis C virus (HCV) sequence variation induces an HCV-specific T-cell phenotype analogous to spontaneous resolution.
Hepatitis C virus (HCV)-specific CD8(+) T cells in persistent HCV infection are low in frequency and paradoxically show a phenotype associated with controlled infections, expressing the memory marker CD127. We addressed to what extent this phenotype is dependent on the presence of cognate antigen. We analyzed virus-specific responses in acute and chronic HCV infections and sequenced autologous virus. We show that CD127 expression is associated with decreased antigenic stimulation after either viral clearance or viral variation. Our data indicate that most CD8 T-cell responses in chronic HCV infection do not target the circulating virus and that the appearance of HCV-specific CD127(+) T cells is driven by viral variation.
Kasprowicz
Victoria
V
Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. vkasprowicz@partners.org
Kang
Yu-Hoi
YH
Lucas
Michaela
M
Schulze zur Wiesch
Julian
J
Kuntzen
Thomas
T
Fleming
Vicki
V
Nolan
Brian E
BE
Longworth
Steven
S
Berical
Andrew
A
Bengsch
Bertram
B
Thimme
Robert
R
Lewis-Ximenez
Lia
L
Allen
Todd M
TM
Kim
Arthur Y
AY
Klenerman
Paul
P
Lauer
Georg M
GM
D000595:Amino Acid Sequence; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000628:therapy / Q000821:virology; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
D053699:Interleukin-7 Receptor alpha Subunit