Upregulation of interleukin 7 receptor alpha and programmed death 1 marks an epitope-specific CD8+ T-cell response that disappears following primary Epstein-Barr virus infection.
In immunocompetent individuals, the stability of the herpesvirus-host balance limits opportunities to study the disappearance of a virus-specific CD8(+) T-cell response. However, we noticed that in HLA-A 0201-positive infectious mononucleosis (IM) patients undergoing primary Epstein-Barr virus (EBV) infection, the initial CD8 response targets three EBV lytic antigen-derived epitopes, YVLDHLIVV (YVL), GLCTLVAML (GLC), and TLDYKPLSV (TLD), but only the YVL and GLC reactivities persist long-term; the TLD response disappears within 10 to 27 months. While present, TLD-specific cells remained largely indistinguishable from YVL and GLC reactivities in many phenotypic and functional respects but showed unique temporal changes in two markers of T-cell fate, interleukin 7 receptor alpha (IL-7Ralpha; CD127) and programmed death 1 (PD-1). Thus, following the antigen-driven downregulation of IL-7Ralpha seen on all populations in acute IM, in every case, the TLD-specific population recovered expression unusually quickly post-IM. As well, in four of six patients studied, TLD-specific cells showed very strong PD-1 upregulation in the last blood sample obtained before the cells' disappearance. Our data suggest that the disappearance of this individual epitope reactivity from an otherwise stable EBV-specific response (i) reflects a selective loss of cognate antigen restimulation (rather than of IL-7-dependent signals) and (ii) is immediately preceded, and perhaps mediated, by PD-1 upregulation to unprecedented levels.
Sauce
Delphine
D
CRUK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Larsen
Martin
M
Abbott
Rachel J M
RJ
Hislop
Andrew D
AD
Leese
Alison M
AM
Khan
Naeem
N
Papagno
Laura
L
Freeman
Gordon J
GJ
Rickinson
Alan B
AB
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis*; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology*
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D000939:Epitopes; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain