Ex vivo detection of adenovirus specific CD4+ T-cell responses to HLA-DR-epitopes of the Hexon protein show a contracted specificity of T(HELPER) cells following stem cell transplantation.
Human adenovirus (HAdV) is a cause of significant morbidity and mortality in immunocompromised patients, especially after stem cell transplantation (SCT). Viral clearance has been attributed to CD4(+) T-cell responses against the Hexon-protein, but the frequency of specific T(HELPER) cells is extremely low or not detectable ex vivo and preference for different CD4(+) T-cell epitopes is variable among individuals. We therefore analyzed 44 healthy donors and 6 SCT-recipients for Hexon-specific CD4(+)-responses ex vivo, to identify epitopes which would be broadly applicable. We selected 19 candidate epitopes with predicted restriction to HLA-DR1/DR3/DR4/DR7; 16 were located within the highly conserved regions, indicating cross-reactivity of T cells among HAdV-subspecies. Ten epitopes induced CD4(+)-proliferation in >50% of individuals, confirmed by intracellular IFN-gamma detection. Three SCT recipients who recovered from an infection with HAdV displayed reactivity towards only a single hexon epitope, whereas healthy individuals were responsive to two to eight epitopes (median 3). The ex vivo detection of Hexon-specific CD4(+) T-cells, without any long-term culture in vitro, enables the detection and generation of HAdV-specific CD4(+) T cells for adoptive T-cell transfer against HAdV-infection post SCT.
Serangeli
Celine
C
Department of Pediatric Hematology/Oncology, University Children's Hospital, Eberhard-Karls University, Hoppe-Seyler Strabetae 1, D-72076 Tübingen, Germany.
Bicanic
Oliver
O
Scheible
Michael H
MH
Wernet
Dorothee
D
Lang
Peter
P
Rammensee
Hans-Georg
HG
Stevanovic
Stefan
S
Handgretinger
Rupert
R
Feuchtinger
Tobias
T
D000260:Adenoviruses, Human / Q000276:immunology*; D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000096:biosynthesis; D033581:Stem Cell Transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; C018315:hexon capsid protein, Adenovirus; D007371:Interferon-gamma