In vitro human CD4+ T cell response to the vaccinia protective antigens B5R and A33R.
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.
Sirven
Philemon
P
CEA, iBiTecS, Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), Gif Sur Yvette F-91191, France.
Castelli
Florence Anne
FA
Probst
Alicia
A
Szely
Natacha
N
Maillere
Bernard
B
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*
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