A HCMV pp65 polypeptide promotes the expansion of CD4+ and CD8+ T cells across a wide range of HLA specificities.
Human cytomegalovirus (HCMV) can cause life-threatening disease in infected hosts. Immunization with human leukocyte antigen (HLA)-restricted immunodominant synthetic peptides and adoptive transfer of epitope-specific T cells have been envisaged to generate or boost HCMV-specific cellular immunity, thereby preventing HCMV infection or reactivation. However, induction or expansion of T cells effective against HCMV are limited by the need of utilizing peptides with defined HLA restrictions. We took advantage of a combination of seven predictive algorithms to identify immunogenic peptides of potential use in the prevention or treatment of HCMV infection or reactivation. Here we describe a pp65-derived peptide (pp65(340-355), RQYDPVAALFFFDIDL: RQY16-mer), characterized by peculiar features. First, RQY-16mer is able to stimulate HCMV pp65 specific responses in both CD4(+) and CD8(+) T cells, restricted by a wide range of HLA class I and II determinants. Second, RQY-16mer is able to induce an unusually wide range of effector functions in CD4(+) T cells, including proliferation, killing of autologous HCMV-infected target cells and cytokine production. Third, and most importantly, the RQY-16mer is able to stimulate CD4(+) and CD8(+) T-cell responses in pharmacologically immunosuppressed patients. These data suggest that a single reagent might qualify as synthetic immunogen for potentially large populations exposed to HCMV infection or reactivation.
Provenzano
Maurizio
M
Institute of Surgical Research and Hospital Management, and Department of Biomedicine, University Hospital Basel, Switzerland.
Sais
Giovanni
G
Institute of Surgical Research and Hospital Management, and Department of Biomedicine, University Hospital Basel, Switzerland.
Bracci
Laura
L
Institute of Surgical Research and Hospital Management, and Department of Biomedicine, University Hospital Basel, Switzerland.
Egli
Adrian
A
Transplantation Virology, Institute for Medical Microbiology, University of Basel, Switzerland.
Anselmi
Maurizio
M
Institute of Surgical Research and Hospital Management, and Department of Biomedicine, University Hospital Basel, Switzerland.
Viehl
Carsten T
CT
Institute of Surgical Research and Hospital Management, and Department of Biomedicine, University Hospital Basel, Switzerland.
Schaub
Stefan
S
Department of Transplantation Immunology and Nephrology, University Hospital Basel, Switzerland.
Hirsch
Hans H
HH
Transplantation Virology, Institute for Medical Microbiology, University of Basel, Switzerland.
Stroncek
David F
DF
Department of Transfusion Medicine, Infectious Diseases and Immunogenetic Section, Clinical Center, NIH, Bethesda, MD, USA.
Marincola
Francesco M
FM
Department of Transfusion Medicine, Infectious Diseases and Immunogenetic Section, Clinical Center, NIH, Bethesda, MD, USA.
Spagnoli
Giulio C
GC
Institute of Surgical Research and Hospital Management, and Department of Biomedicine, University Hospital Basel, Switzerland.
D000465:Algorithms; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017931:DNA Primers; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D016133:Polymerase Chain Reaction; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000502:physiology*
D017931:DNA Primers; D006680:HLA Antigens; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa