PMID- 28085643
OWN - NLM
STAT- MEDLINE
DCOM- 20180102
LR  - 20180124
IS  - 1557-8976 (Electronic)
IS  - 0882-8245 (Linking)
VI  - 30
IP  - 3
DP  - 2017 Apr
TI  - Presentation of a Conserved Adenoviral Epitope on HLA-C*0702 Allows Evasion of 
      Natural Killer but Not T Cell Responses.
PG  - 149-156
LID - 10.1089/vim.2016.0145 [doi]
AB  - Infection with adenovirus is a major cause of infectious mortality in children 
      following hematopoietic stem-cell transplantation. While adoptive transfer of 
      epitope-specific T cells is a particularly effective therapeutic approach, there 
      are few suitable adenoviral peptide epitopes described to date. Here, we describe 
      the adenoviral peptide epitope FRKDVNMVL from hexon protein, and its variant 
      FRKDVNMIL, that is restricted by human leukocyte antigen (HLA)-C*0702. Since 
      HLA-C*0702 can be recognized by both T cells and natural killer (NK) cells, we 
      characterized responses by both cell types. T cells specific for FRKDVNMVL were 
      detected in peripheral blood mononuclear cells expanded from eight of ten healthy 
      HLA-typed donors by peptide-HLA multimer staining, and could also be detected by 
      cultured interferon gamma ELISpot assays. Surprisingly, HLA-C*0702 was not 
      downregulated during infection, in contrast to the marked downregulation of 
      HLA-A*0201, suggesting that adenovirus cannot evade T cell responses to 
      HLA-C*0702-restricted peptide epitopes. By contrast, NK responses were inhibited 
      following adenoviral peptide presentation. Notably, presentation of the FRKDVNMVL 
      peptide enhanced binding of HLA-C*0702 to the inhibitory receptor KIR2DL3 and 
      decreased NK cytotoxic responses, suggesting that adenoviruses may use this 
      peptide to evade NK responses. Given the immunodominance of FRKDVNMVL-specific T 
      cell responses, apparent lack of HLA-C*0702 downregulation during infection, and 
      the high frequency of this allotype, this peptide epitope may be particularly 
      useful for adoptive T cell transfer therapy of adenovirus infection.
FAU - Keib, Anna
AU  - Keib A
AD  - 1 Institute for Medical Virology, University Hospital Tubingen , Tubingen, 
      Germany .
FAU - Gunther, Patrick S
AU  - Gunther PS
AD  - 1 Institute for Medical Virology, University Hospital Tubingen , Tubingen, 
      Germany .
FAU - Faist, Benjamin
AU  - Faist B
AD  - 2 Institute for Medical Microbiology, Immunology and Hygiene, Technical 
      University Munich , Munich, Germany .
FAU - Halenius, Anne
AU  - Halenius A
AD  - 3 Institute of Virology, University Hospital Freiburg , Freiburg, Germany .
FAU - Busch, Dirk H
AU  - Busch DH
AD  - 2 Institute for Medical Microbiology, Immunology and Hygiene, Technical 
      University Munich , Munich, Germany .
AD  - 4 German Center for Infection Research (DZIF) , Partner Sites Tubingen and 
      Munich, Germany .
FAU - Neuenhahn, Michael
AU  - Neuenhahn M
AD  - 2 Institute for Medical Microbiology, Immunology and Hygiene, Technical 
      University Munich , Munich, Germany .
AD  - 4 German Center for Infection Research (DZIF) , Partner Sites Tubingen and 
      Munich, Germany .
FAU - Jahn, Gerhard
AU  - Jahn G
AD  - 1 Institute for Medical Virology, University Hospital Tubingen , Tubingen, 
      Germany .
FAU - Dennehy, Kevin M
AU  - Dennehy KM
AD  - 1 Institute for Medical Virology, University Hospital Tubingen , Tubingen, 
      Germany .
AD  - 4 German Center for Infection Research (DZIF) , Partner Sites Tubingen and 
      Munich, Germany .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170113
PL  - United States
TA  - Viral Immunol
JT  - Viral immunology
JID - 8801552
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-C Antigens)
SB  - IM
MH  - Adenoviruses, Human/*immunology
MH  - *Antigen Presentation
MH  - Epitopes, T-Lymphocyte/immunology/*metabolism
MH  - HLA-C Antigens/*metabolism
MH  - Humans
MH  - *Immune Evasion
MH  - Killer Cells, Natural/*immunology
MH  - T-Lymphocytes/*immunology
OTO - NOTNLM
OT  - adenovirus
OT  - adoptive transfer therapy
OT  - immunoevasion
OT  - peptide epitope
EDAT- 2017/01/14 06:00
MHDA- 2018/01/03 06:00
CRDT- 2017/01/14 06:00
PHST- 2017/01/14 06:00 [pubmed]
PHST- 2018/01/03 06:00 [medline]
PHST- 2017/01/14 06:00 [entrez]
AID - 10.1089/vim.2016.0145 [doi]
PST - ppublish
SO  - Viral Immunol. 2017 Apr;30(3):149-156. doi: 10.1089/vim.2016.0145. Epub 2017 Jan 
      13.