title: In vitro human CD4+ T cell response to the vaccinia protective antigens B5R and A33R.
abstract: Subunit vaccine candidates against poxvirus infection induced protective humoral and cellular response in animal models but their immunogenicity in human remains unknown. We have therefore evaluated in vitro the CD4 T cell response of the major antigens B5R and A33R and characterized their CD4 T cell epitopes. Twelve peptides selected on the basis of their binding capacity to HLA-DR molecules, induced CD4 T lymphocytes harvested in healthy donors. In the A33R proteins two peptides are T cell stimulating for at least half of the donors and are restricted to multiple HLA-DR molecules in agreement with their broad specificity for HLA-DR molecules. In B5R, two peptides exhibited a good immunoprevalence but only one is a good binder to multiple HLA-DR molecules. One peptide was a moderate binder for multiple HLA-DR molecules, although it was efficiently presented to peptide-specific T cell lines. Altogether, our data demonstrated the capacity of B5R and A33R peptides to elicit a T cell response in multiple healthy donors and showed that promiscuity and immunoprevalence of CD4 T cell epitopes are not necessarily associated.
authors.affiliation: CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Gif Sur Yvette F-91191, France.
authors.forename: Philemon
authors.initials: P
authors.lastname: Sirven
authors.forename: Florence Anne
authors.initials: FA
authors.lastname: Castelli
authors.forename: Alicia
authors.initials: A
authors.lastname: Probst
authors.forename: Natacha
authors.initials: N
authors.lastname: Szely
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillere
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D013379:Substrate Specificity; D014613:Vaccines, Attenuated / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: C446940:A33R protein, Vaccinia virus; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; C074512:42kDa protein, Vaccinia virus