PMID- 12559623
OWN - NLM
STAT- MEDLINE
DCOM- 20030926
LR  - 20190906
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 64
IP  - 2
DP  - 2003 Feb
TI  - Derivation of HLA-B*0702 transgenic mice: functional CTL repertoire and 
      recognition of human B*0702-restricted CTL epitopes.
PG  - 211-23
AB  - Transgenic mice expressing chimeric human leukocyte antigen (HLA)-B*0702 and 
      murine H-2K(b) class I molecules were evaluated as a model system to study the 
      immunogenicity of human cytotoxic T lymphocyte epitopes. Immunization of these 
      mice with six known HLA-B*0702-restricted cytotoxic T lymphocyte epitopes 
      emulsified in incomplete Freund's adjuvant induced significant immune responses 
      specific for all six epitopes. A comparison of the immune responses between 
      HLA-B*0702/K(b) and HLA-A*0201/K(b) transgenic mice demonstrated that the 
      HLA-B*0702/K(b) mice possess a T-cell receptor repertoire capable of recognizing 
      human B*0702 epitopes. However, the magnitude of B*0702-specific responses 
      induced in B*0702/K(b) mice were approximately tenfold lower than A*0201-specific 
      responses induced in HLA-A*0201/K(b) transgenic mice. A panel of 24 B*0702 
      motif-bearing peptides was used to examine the relationship between 
      immunogenicity and HLA-B*0702 binding capacity. All seven peptides with high 
      binding affinities of 50% inhibitory concentration < or =50 NM (IC(50) 50 nM or 
      less) were immunogenic. Similarly, 75% (9 of 12) of the intermediate binders 
      (IC(50) nM of 50-500) were also immunogenic. Finally, only two of five peptides 
      with binding capacity > 500 nM were found to have marginal immunogenicity, 
      whereas the other three were completely negative. HLA-B*0702/K(b) transgenic mice 
      were found to induce B*0702-specific responses after immunization with whole DNA 
      genes or minigenes, suggesting that, at least to some degree, B*0702 epitopes 
      were generated as a result of natural in vivo processing and presentation.
FAU - Alexander, Jeff
AU  - Alexander J
AD  - Epimmune Inc., San Diego, California 92121, USA. jalexander@epimmune.com
FAU - Oseroff, Carla
AU  - Oseroff C
FAU - Sidney, John
AU  - Sidney J
FAU - Sette, Alessandro
AU  - Sette A
LA  - eng
GR  - N01-A1-95362/PHS HHS/United States
GR  - N01-AI-45241/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (H-2 Antigens)
RN  - 0 (H-2Kb protein, mouse)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*07:02 antigen)
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigen Presentation
MH  - Cell Line
MH  - Cytotoxicity, Immunologic
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Genes, MHC Class I
MH  - Genes, Synthetic
MH  - H-2 Antigens/genetics/immunology
MH  - HLA-A Antigens/genetics/immunology
MH  - HLA-A2 Antigen
MH  - HLA-B Antigens/*genetics/immunology
MH  - HLA-B7 Antigen
MH  - Humans
MH  - Immunization
MH  - Immunodominant Epitopes/immunology
MH  - Interferon-gamma/metabolism
MH  - Jurkat Cells
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Peptide Fragments/immunology
MH  - Recombinant Fusion Proteins/genetics/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2003/02/01 04:00
MHDA- 2003/09/27 05:00
CRDT- 2003/02/01 04:00
PHST- 2003/02/01 04:00 [pubmed]
PHST- 2003/09/27 05:00 [medline]
PHST- 2003/02/01 04:00 [entrez]
AID - S0198885902007863 [pii]
AID - 10.1016/s0198-8859(02)00786-3 [doi]
PST - ppublish
SO  - Hum Immunol. 2003 Feb;64(2):211-23. doi: 10.1016/s0198-8859(02)00786-3.