PMID- 19845536 OWN - NLM STAT- MEDLINE DCOM- 20091202 LR - 20211020 IS - 1600-0463 (Electronic) IS - 0903-4641 (Print) IS - 0903-4641 (Linking) VI - 117 IP - 11 DP - 2009 Nov TI - Immune hierarchy among HIV-1 CD8+ T cell epitopes delivered by dendritic cells depends on MHC-I binding irrespective of mode of loading and immunization in HLA-A*0201 mice. PG - 849-55 LID - 10.1111/j.1600-0463.2009.02544.x [doi] AB - Recent human immunodeficiency virus type 1 (HIV-1) vaccination strategies aim at targeting a broad range of cytotoxic T lymphocyte (CTL) epitopes from different HIV-1 proteins by immunization with multiple CTL epitopes simultaneously. However, this may establish an immune hierarchical response, where the immune system responds to only a small number of the epitopes administered. To evaluate the feasibility of such vaccine strategies, we used the human leukocyte antigen (HLA)-A*0201 transgenic (tg) HHD murine in vivo model and immunized with dendritic cells pulsed with seven HIV-1-derived HLA-A*0201 binding CTL epitopes. The seven peptides were simultaneously presented on the same dendritic cell (DC) or on separate DCs before immunization to one or different lymphoid compartments. Data from this study showed that the T-cell response, as measured by cytolytic activity and gamma-interferon (IFN-gamma)-producing CD8(+) T cells, mainly focused on two of seven administered epitopes. The magnitude of individual T-cell responses induced by immunization with multiple peptides correlated with their individual immunogenicity that depended on major histocompatibility class I binding and was not influenced by mode of loading or mode of immunization. These findings may have implications for the design of vaccines based on DCs when using multiple epitopes simultaneously. FAU - Kloverpris, Henrik N AU - Kloverpris HN AD - Department of Virology, Statens Serum Institut, Copenhagen, Denmark. FAU - Karlsson, Ingrid AU - Karlsson I FAU - Thorn, Mette AU - Thorn M FAU - Buus, Soren AU - Buus S FAU - Fomsgaard, Anders AU - Fomsgaard A LA - eng PT - Journal Article PL - Denmark TA - APMIS JT - APMIS : acta pathologica, microbiologica, et immunologica Scandinavica JID - 8803400 RN - 0 (AIDS Vaccines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A*02:01 antigen) RN - 0 (HLA-A2 Antigen) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - AIDS Vaccines/*immunology/standards MH - Animals MH - CD8-Positive T-Lymphocytes/*immunology MH - Dendritic Cells/immunology/virology MH - Enzyme-Linked Immunosorbent Assay MH - Epitopes, T-Lymphocyte/*immunology MH - Flow Cytometry MH - HIV Infections/*immunology/prevention & control MH - HIV-1/*immunology MH - HLA-A Antigens/*immunology MH - HLA-A2 Antigen MH - Interferon-gamma/immunology MH - Mice MH - Mice, Transgenic MH - T-Lymphocytes, Cytotoxic/immunology/virology PMC - PMC2774155 EDAT- 2009/10/23 06:00 MHDA- 2009/12/16 06:00 CRDT- 2009/10/23 06:00 PHST- 2009/10/23 06:00 [entrez] PHST- 2009/10/23 06:00 [pubmed] PHST- 2009/12/16 06:00 [medline] AID - APM2544 [pii] AID - 10.1111/j.1600-0463.2009.02544.x [doi] PST - ppublish SO - APMIS. 2009 Nov;117(11):849-55. doi: 10.1111/j.1600-0463.2009.02544.x.