PMID- 29084215
OWN - NLM
STAT- MEDLINE
DCOM- 20171212
LR  - 20181113
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 11
IP  - 10
DP  - 2017 Oct
TI  - Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from 
      Chikungunya 6K protein.
PG  - e0006036
LID - 10.1371/journal.pntd.0006036 [doi]
LID - e0006036
AB  - BACKGROUND: The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is 
      critical for clearance of many viral infections. These CTL recognize naturally 
      processed short viral antigenic peptides bound to human leukocyte antigen (HLA) 
      class I molecules on the surface of infected cells. This specific recognition 
      allows the killing of virus-infected cells. The T cell immune T cell response to 
      Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family 
      responsible for severe musculoskeletal disorders, has not been fully defined; 
      nonetheless, the importance of HLA class I-restricted immune response in this 
      virus has been hypothesized. METHODOLOGY/PRINCIPAL FINDINGS: By infection of 
      HLA-A*0201-transgenic mice with a recombinant vaccinia virus that encodes the 
      CHIKV structural polyprotein (rVACV-CHIKV), we identified the first human T cell 
      epitopes from CHIKV. These three novel 6K transmembrane protein-derived epitopes 
      are presented by the common HLA class I molecule, HLA-A*0201. One of these 
      epitopes is processed and presented via a complex pathway that involves proteases 
      from different subcellular locations. Specific chemical inhibitors blocked these 
      events in rVACV-CHIKV-infected cells. CONCLUSIONS/SIGNIFICANCE: Our data have 
      implications not only for the identification of novel Alphavirus and Togaviridae 
      antiviral CTL responses, but also for analyzing presentation of antigen from 
      viruses of different families and orders that use host proteinases to generate 
      their mature envelope proteins.
FAU - Lorente, Elena
AU  - Lorente E
AD  - Unidad de Procesamiento Antigenico, Centro Nacional de Microbiologia, Instituto 
      de Salud Carlos III, Majadahonda, Madrid, Spain.
FAU - Barriga, Alejandro
AU  - Barriga A
AD  - Unidad de Procesamiento Antigenico, Centro Nacional de Microbiologia, Instituto 
      de Salud Carlos III, Majadahonda, Madrid, Spain.
FAU - Garcia-Arriaza, Juan
AU  - Garcia-Arriaza J
AD  - Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, 
      Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.
FAU - Lemonnier, Francois A
AU  - Lemonnier FA
AD  - Unite d'Immunite Cellulaire Antivirale, Departement d'Immunologie, Institut 
      Pasteur, France.
FAU - Esteban, Mariano
AU  - Esteban M
AD  - Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, 
      Consejo Superior de Investigaciones Cientificas (CSIC), Madrid, Spain.
FAU - Lopez, Daniel
AU  - Lopez D
AUID- ORCID: 0000-0003-0268-5878
AD  - Unidad de Procesamiento Antigenico, Centro Nacional de Microbiologia, Instituto 
      de Salud Carlos III, Majadahonda, Madrid, Spain.
LA  - eng
PT  - Journal Article
DEP - 20171030
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Animals
MH  - *Antigen Presentation
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Chikungunya Fever/genetics/*immunology/virology
MH  - Chikungunya virus/chemistry/genetics/*immunology
MH  - Epitopes, T-Lymphocyte/chemistry/genetics/*immunology
MH  - HLA-A Antigens/chemistry/genetics/*immunology
MH  - HLA-A2 Antigen/*immunology
MH  - Humans
MH  - Mice
MH  - Viral Proteins/chemistry/genetics/*immunology
PMC - PMC5679651
COIS- The authors have declared that no competing interests exist.
EDAT- 2017/10/31 06:00
MHDA- 2017/12/13 06:00
PMCR- 2017/10/30
CRDT- 2017/10/31 06:00
PHST- 2017/07/25 00:00 [received]
PHST- 2017/10/13 00:00 [accepted]
PHST- 2017/11/09 00:00 [revised]
PHST- 2017/10/31 06:00 [pubmed]
PHST- 2017/12/13 06:00 [medline]
PHST- 2017/10/31 06:00 [entrez]
PHST- 2017/10/30 00:00 [pmc-release]
AID - PNTD-D-17-01168 [pii]
AID - 10.1371/journal.pntd.0006036 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2017 Oct 30;11(10):e0006036. doi: 
      10.1371/journal.pntd.0006036. eCollection 2017 Oct.