PMID- 29698425
OWN - NLM
STAT- MEDLINE
DCOM- 20180724
LR  - 20201214
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 4
DP  - 2018
TI  - Complexity of type-specific 56 kDa antigen CD4 T-cell epitopes of Orientia 
      tsutsugamushi strains causing scrub typhus in India.
PG  - e0196240
LID - 10.1371/journal.pone.0196240 [doi]
LID - e0196240
AB  - Orientia tsutsugamushi (Ots) is an obligate, intracellular, mite-transmitted 
      human pathogen which causes scrub typhus. Understanding the diversity of Ots 
      antigens is essential for designing specific diagnostic assays and efficient 
      vaccines. The protective immunodominant type-specific 56 kDa antigen (TSA) of Ots 
      varies locally and across its geographic distribution. TSA contains four 
      hypervariable domains. We bioinformatically analyzed 345 partial sequences of TSA 
      available from India, most of which contain only the three variable domains 
      (VDI-III) and three spacer conserved domains (SVDI, SVDII/III, SVDIII). The total 
      number (152) of antigenic types (amino acid variants) varied from 14-36 in the 
      six domains of TSA that we studied. Notably, 55% (787/1435) of the predicted CD4 
      T-cell epitopes (TCEs) from all the six domains had high binding affinities (HBA) 
      to at least one of the prevalent Indian human leukocyte antigen (HLA) alleles. A 
      surprisingly high proportion (61%) of such TCEs were from spacer domains; indeed 
      100% of the CD4 TCEs in the SVDI were HBA. TSA sequences from India had more 
      antigenic types (AT) than TSA from Korea. Overall, >90% of predicted CD4 TCEs 
      from spacer domains were predicted to have HBA against one or more prevalent HLA 
      types from Indian, Korean, Asia-Pacific region or global population data sets, 
      while only <50% of CD4 TCEs in variable domains exhibited such HBA. The 
      phylogenetically and immunologically important amino acids in the conserved 
      spacer domains were identified. Our results suggest that the conserved spacer 
      domains are predicted to be functionally more important than previously 
      appreciated in immune responses to Ots infections. Changes occurring at the TCE 
      level of TSA may contribute to the wide range of pathogenicity of Ots in humans 
      and mouse models. CD4 T-cell functional experiments are needed to assess the 
      immunological significance of these HBA spacer domains and their role in 
      clearance of Ots from Indian patients.
FAU - Ramaiah, Arunachalam
AU  - Ramaiah A
AUID- ORCID: 0000-0003-3573-6141
AD  - Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, 
      GA, United States.
FAU - Koralur, Munegowda C
AU  - Koralur MC
AUID- ORCID: 0000-0001-6347-3890
AD  - Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, 
      GA, United States.
FAU - Dasch, Gregory A
AU  - Dasch GA
AD  - Rickettsial Zoonoses Branch, Centers for Disease Control and Prevention, Atlanta, 
      GA, United States.
LA  - eng
GR  - U60 OE000103/OE/OSELS CDC HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20180426
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Antigens, Bacterial/chemistry/immunology/*metabolism
MH  - Epitopes, T-Lymphocyte/chemistry/classification/*metabolism
MH  - Evolution, Molecular
MH  - HLA-DRB1 Chains/genetics/metabolism
MH  - Humans
MH  - India
MH  - Orientia tsutsugamushi/*metabolism
MH  - Phylogeny
MH  - Protein Binding
MH  - Protein Domains
MH  - Scrub Typhus/*diagnosis/microbiology
MH  - Sequence Alignment
PMC - PMC5919512
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2018/04/27 06:00
MHDA- 2018/07/25 06:00
PMCR- 2018/04/26
CRDT- 2018/04/27 06:00
PHST- 2018/01/31 00:00 [received]
PHST- 2018/04/09 00:00 [accepted]
PHST- 2018/04/27 06:00 [entrez]
PHST- 2018/04/27 06:00 [pubmed]
PHST- 2018/07/25 06:00 [medline]
PHST- 2018/04/26 00:00 [pmc-release]
AID - PONE-D-18-03360 [pii]
AID - 10.1371/journal.pone.0196240 [doi]
PST - epublish
SO  - PLoS One. 2018 Apr 26;13(4):e0196240. doi: 10.1371/journal.pone.0196240. 
      eCollection 2018.