A recombinant human HLA-class I antigen linked to dextran elicits innate and adaptive immune responses.
The objective of this study was to produce and evaluate the immunogenic potential of a recombinant HLA-class I antigen linked to dextran. The HLA-A*0201 heavy chain and beta2 microglobulin were cloned by PCR amplification of overlapping oligonucleotides and produced in E. coli. These were assembled with a CMV binding peptide motif, the HLA complex was biotinylated and bound by streptavidin coated dextran at a ratio of 24 HLA to 1 dextran molecule (termed Dextramer). Allostimulation of human PBMC in vitro and in vivo immunization of Balb c mice with the HLA-A*0201 construct elicited CD4+ and CD8+ T cell proliferative responses, IgG specific antibodies in mice and in human T cell proliferation and APOBEC3G mRNA. These adaptive and innate immune responses induced by a novel recombinant HLA construct in human cells and mice suggest their application as a potential vaccine candidate against HIV infection.
Schøller
Jorgen
J
Immudex, Copenhagen, Denmark.
Singh
Mahavir
M
Bergmeier
Lesley
L
Brunstedt
Katja
K
Wang
Yufei
Y
Whittall
Trevor
T
Rahman
Durdana
D
Pido-Lopez
J
J
Lehner
T
T
D016915:AIDS Vaccines; D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003911:Dextrans / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015789:HLA-A2 Antigen; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D016915:AIDS Vaccines; D003911:Dextrans; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D011994:Recombinant Proteins