PMID- 31276466 OWN - NLM STAT- MEDLINE DCOM- 20200107 LR - 20200309 IS - 1935-2735 (Electronic) IS - 1935-2727 (Print) IS - 1935-2727 (Linking) VI - 13 IP - 7 DP - 2019 Jul TI - Immunoproteomic analysis of a Chikungunya poxvirus-based vaccine reveals high HLA class II immunoprevalence. PG - e0007547 LID - 10.1371/journal.pntd.0007547 [doi] LID - e0007547 AB - BACKGROUND: Efficient adaptive antiviral cellular and humoral immune responses require previous recognition of viral antigenic peptides bound to human leukocyte antigen (HLA) class I and II molecules, which are exposed on the surface of infected and antigen presenting cells, respectively. The HLA-restricted immune response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe chronic polyarthralgia and polyarthritis, is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a high-throughput mass spectrometry analysis of complex HLA-bound peptide pools isolated from large amounts of human cells infected with a vaccinia virus (VACV) recombinant expressing CHIKV structural proteins was carried out. Twelve viral ligands from the CHIKV polyprotein naturally presented by different HLA-A, -B, and -C class I, and HLA-DR and -DP class II molecules were identified. CONCLUSIONS/SIGNIFICANCE: The immunoprevalence of the HLA class II but not the HLA class I-restricted cellular immune response against the CHIKV structural polyprotein was greater than that against the VACV vector itself. In addition, most of the CHIKV HLA class I and II ligands detected by mass spectrometry are not conserved compared to its closely related O'nyong-nyong virus. These findings have clear implications for analysis of both cytotoxic and helper immune responses against CHIKV as well as for the future studies focused in the exacerbated T helper response linked to chronic musculoskeletal disorders in CHIKV patients. FAU - Lorente, Elena AU - Lorente E AD - Unidad de Presentacion y Regulacion Inmunes, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda (Madrid), Spain. FAU - Barriga, Alejandro AU - Barriga A AD - Unidad de Presentacion y Regulacion Inmunes, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda (Madrid), Spain. FAU - Barnea, Eilon AU - Barnea E AD - Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel. FAU - Palomo, Concepcion AU - Palomo C AD - Unidad de Presentacion y Regulacion Inmunes, 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 - Mir, Carmen AU - Mir C AD - Unidad de Presentacion y Regulacion Inmunes, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda (Madrid), Spain. 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 - Admon, Arie AU - Admon A AD - Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel. FAU - Lopez, Daniel AU - Lopez D AUID- ORCID: 0000-0003-0268-5878 AD - Unidad de Presentacion y Regulacion Inmunes, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda (Madrid), Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190705 PL - United States TA - PLoS Negl Trop Dis JT - PLoS neglected tropical diseases JID - 101291488 RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Viral Proteins) RN - 0 (Viral Vaccines) SB - IM MH - Animals MH - Animals, Genetically Modified MH - Antigen Presentation MH - Antigen-Presenting Cells/immunology MH - Chikungunya Fever/immunology/*prevention & control MH - Chikungunya virus MH - Histocompatibility Antigens Class II/*immunology MH - Humans MH - Immunity, Cellular MH - Immunogenicity, Vaccine MH - Mass Spectrometry MH - Mice MH - *Proteomics MH - T-Lymphocytes, Cytotoxic/immunology MH - T-Lymphocytes, Helper-Inducer/immunology MH - *Vaccinia virus MH - Viral Proteins/*immunology MH - Viral Vaccines/genetics/*immunology PMC - PMC6636782 COIS- The authors have declared that no competing interests exist. EDAT- 2019/07/06 06:00 MHDA- 2020/01/08 06:00 PMCR- 2019/07/05 CRDT- 2019/07/06 06:00 PHST- 2019/02/06 00:00 [received] PHST- 2019/06/11 00:00 [accepted] PHST- 2019/07/17 00:00 [revised] PHST- 2019/07/06 06:00 [pubmed] PHST- 2020/01/08 06:00 [medline] PHST- 2019/07/06 06:00 [entrez] PHST- 2019/07/05 00:00 [pmc-release] AID - PNTD-D-19-00186 [pii] AID - 10.1371/journal.pntd.0007547 [doi] PST - epublish SO - PLoS Negl Trop Dis. 2019 Jul 5;13(7):e0007547. doi: 10.1371/journal.pntd.0007547. eCollection 2019 Jul.