PMID- 18353510
OWN - NLM
STAT- MEDLINE
DCOM- 20080924
LR  - 20080613
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 26
IP  - 25
DP  - 2008 Jun 13
TI  - Assessing vaccine potency using TCRmimic antibodies.
PG  - 3092-102
LID - 10.1016/j.vaccine.2008.02.025 [doi]
AB  - Dendritic cells (DCs) are highly specialized antigen-presenting cells of the 
      immune system that are efficient at presenting peptide-antigen for the activation 
      of T cells and are often the cell type of choice for vaccine targeting by virtue 
      of high expression levels of MHC and costimulatory molecules. Since the level of 
      peptide-MHC complex significantly influences stimulation of T cells, a 
      proof-of-concept potency assay was developed to directly examine the presentation 
      and density of MHC class I peptides derived from the processing of a model tumor 
      antigen, (hCGbeta), on the surface of DCs. In this study we first generated 
      antibodies (TCR mimics or TCRm) to two peptide-HLA-A*0201 epitopes derived from 
      hCGbeta designated as TMT (40-48) and GVL (47-55). Characterization of each TCRm 
      by ELISA and flow cytometric analysis, demonstrated specific binding to soluble 
      recombinant HLA-A2 protein and HLA-A2.1+ T2 cells loaded with relevant peptide. 
      TCRm reactive against the TMT and GVL epitopes blocked granzyme-B production by 
      peptide-specific cytotoxic T lymphocytes (CTL) lines further supporting their 
      recognition specificity. For the assessment of antigen presentation function, 
      human immature monocyte-derived DCs (iDCs) were treated with the mannose receptor 
      targeting vaccine, B11-hCGbeta and matured with Poly I:C. The TMT and GVL epitope 
      reactive CTL lines responded to vaccine-treated but not vehicle-treated mature 
      DCs (mDCs) with TMT and GVL TCRm specifically blocking IFN-gamma production. The 
      TCRm were then used to directly confirm specific peptide-MHC complexes on mDCs. 
      TCRm staining of vaccine-treated mDCs showed detection of the TMT and GVL 
      peptide-HLA-A2 complexes. These findings demonstrate that TCRms may be important 
      tools for determining the potency of DC-based vaccines.
FAU - Neethling, Francisca A
AU  - Neethling FA
AD  - Receptor Logic Ltd., Abilene, TX 79601, United States.
FAU - Ramakrishna, Venky
AU  - Ramakrishna V
FAU - Keler, Tibor
AU  - Keler T
FAU - Buchli, Rico
AU  - Buchli R
FAU - Woodburn, Tito
AU  - Woodburn T
FAU - Weidanz, Jon A
AU  - Weidanz JA
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080225
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Antibodies, Monoclonal/*administration & dosage/immunology
MH  - Antibody Specificity
MH  - Antigens, Neoplasm/*immunology
MH  - Cancer Vaccines/*administration & dosage/immunology
MH  - Cell Line
MH  - Dendritic Cells/immunology
MH  - Epitopes/*immunology/metabolism
MH  - HLA-A2 Antigen/genetics/*immunology
MH  - Humans
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2008/03/21 09:00
MHDA- 2008/09/25 09:00
CRDT- 2008/03/21 09:00
PHST- 2008/03/21 09:00 [pubmed]
PHST- 2008/09/25 09:00 [medline]
PHST- 2008/03/21 09:00 [entrez]
AID - S0264-410X(08)00154-0 [pii]
AID - 10.1016/j.vaccine.2008.02.025 [doi]
PST - ppublish
SO  - Vaccine. 2008 Jun 13;26(25):3092-102. doi: 10.1016/j.vaccine.2008.02.025. Epub 
      2008 Feb 25.