Antigenic properties of HCMV peptides displayed by filamentous bacteriophages vs. synthetic peptides.
Several efforts have been invested in the identification of CTL and Th epitopes, as well as in the characterization of their immunodominance and MHC restriction, for the generation of a peptide-based HCMV vaccine. Small synthetic peptides are, however, poor antigens and carrier proteins are important for improving the efficacy of synthetic peptide vaccines. Recombinant bacteriophages appear as promising tools in the design of subunit vaccines. To investigate the antigenicity of peptides carried by recombinant bacteriophages we displayed different HCMV MHCII restricted peptides on the capsid of filamentous bacteriophage (fd) and found that hybrid bacteriophages are processed by human APC and activate HCMV-specific CD4 T-cells. Furthermore we constructed a reporter T-cell hybridoma expressing a chimeric TCR comprising murine alphabeta constant regions and human variable regions specific for the HLA-A2 restricted immunodominant NLV peptide of HCMV. Using the filamentous bacteriophage as an epitope carrier, we detected a more robust and long lasting response of the reporter T-cell hybridoma compared to peptide stimulation. Our results show a general enhancement of T-cell responses when antigenic peptides are carried by phages.
Department of Evolutionary Biology, University of Siena, Via A. Moro 2, 53100 Siena, Italy.
Cristina
C
Ulivieri
Alessandra
A
Citro
Federico
F
Ivaldi
Dina
D
Mascolo
Raffaella
R
Ghittoni
Daniela
D
Fanigliulo
Fabrizio
F
Manca
Cosima Tatiana
CT
Baldari
Giuseppina
G
Li Pira
Giovanna
G
Del Pozzo
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D017912:Inovirus / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000235:genetics; D014162:Transfection; D019076:Transgenes / Q000235:genetics; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D037181:Lectins, C-Type; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D000099192:CD69 Antigens