PMID- 20195541
OWN - NLM
STAT- MEDLINE
DCOM- 20100930
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 2
DP  - 2010 Feb 25
TI  - Helper T cell epitope-mapping reveals MHC-peptide binding affinities that 
      correlate with T helper cell responses to pneumococcal surface protein A.
PG  - e9432
LID - 10.1371/journal.pone.0009432 [doi]
LID - e9432
AB  - Understanding the requirements for protection against pneumococcal carriage and 
      pneumonia will greatly benefit efforts in controlling these diseases. Several 
      proteins and polysaccharide capsule have recently been implicated in the 
      virulence of and protective immunity against Streptococcus pneumonia. 
      Pneumococcal surface protein A (PspA) is highly conserved among S. pneumonia 
      strains, inhibits complement activation, binds lactoferrin, elicits protective 
      systemic immunity against pneumococcal infection, and is necessary for full 
      pneumococcal virulence. Identification of PspA peptides that optimally bind human 
      leukocyte antigen (HLA) would greatly contribute to global vaccine efforts, but 
      this is hindered by the multitude of HLA polymorphisms. Here, we have used an 
      experimental data set of 54 PspA peptides and in silico methods to predict 
      peptide binding to HLA and murine major histocompatibility complex (MHC) class 
      II. We also characterized spleen- and cervical lymph node (CLN)-derived helper T 
      lymphocyte (HTL) cytokine responses to these peptides after S. pneumonia strain 
      EF3030-challenge in mice. Individual, yet overlapping peptides, 15 amino acids in 
      length revealed residues 199 to 246 of PspA (PspA(199-246)) consistently caused 
      the greatest IFN-gamma, IL-2, IL-5 and proliferation as well as moderate IL-10 
      and IL-4 responses by ex vivo stimulated splenic and CLN CD4(+) T cells isolated 
      from S. pneumonia strain EF3030-challeged F(1) (B6xBALB/c) mice. IEDB, RANKPEP, 
      SVMHC, MHCPred, and SYFPEITHI in silico analysis tools revealed peptides in 
      PspA(199-246) also interact with a broad range of HLA-DR, -DQ, and -DP allelles. 
      These data suggest that predicted MHC class II-peptide binding affinities do not 
      always correlate with T helper (Th) cytokine or proliferative responses to PspA 
      peptides, but when used together with in vivo validation can be a useful tool to 
      choose candidate pneumococcal HTL epitopes.
FAU - Singh, Rajesh
AU  - Singh R
AD  - Department of Microbiology, Biochemistry, and Immunology, Morehouse School of 
      Medicine, Atlanta, Georgia, United States of America.
FAU - Singh, Shailesh
AU  - Singh S
FAU - Sharma, Praveen K
AU  - Sharma PK
FAU - Singh, Udai P
AU  - Singh UP
FAU - Briles, David E
AU  - Briles DE
FAU - Hollingshead, Susan K
AU  - Hollingshead SK
FAU - Lillard, James W Jr
AU  - Lillard JW Jr
LA  - eng
GR  - G12 RR003034/RR/NCRR NIH HHS/United States
GR  - MD00525/MD/NIMHD NIH HHS/United States
GR  - P60 MD000525/MD/NIMHD NIH HHS/United States
GR  - AI057808/AI/NIAID NIH HHS/United States
GR  - GM09248/GM/NIGMS NIH HHS/United States
GR  - RR03034/RR/NCRR NIH HHS/United States
GR  - R01 AI057808/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100225
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bacterial Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptides)
RN  - 0 (pneumococcal surface protein A)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Bacterial Proteins/*immunology/metabolism
MH  - Binding, Competitive
MH  - CD4-Positive T-Lymphocytes/cytology/immunology/metabolism
MH  - Cell Proliferation
MH  - Cytokines/metabolism
MH  - Epitope Mapping
MH  - Epitopes, T-Lymphocyte/*immunology/metabolism
MH  - Female
MH  - Histocompatibility Antigens/genetics/immunology/metabolism
MH  - Histocompatibility Antigens Class II/genetics/immunology/metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred Strains
MH  - Molecular Sequence Data
MH  - Peptides/genetics/*immunology/metabolism
MH  - Pneumococcal Infections/immunology/microbiology
MH  - Protein Binding
MH  - Streptococcus pneumoniae/genetics/immunology/metabolism
MH  - T-Lymphocytes, Helper-Inducer/cytology/*immunology/metabolism
PMC - PMC2828482
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/03/03 06:00
MHDA- 2010/10/01 06:00
PMCR- 2010/02/25
CRDT- 2010/03/03 06:00
PHST- 2009/09/10 00:00 [received]
PHST- 2010/02/02 00:00 [accepted]
PHST- 2010/03/03 06:00 [entrez]
PHST- 2010/03/03 06:00 [pubmed]
PHST- 2010/10/01 06:00 [medline]
PHST- 2010/02/25 00:00 [pmc-release]
AID - 09-PONE-RA-12807R1 [pii]
AID - 10.1371/journal.pone.0009432 [doi]
PST - epublish
SO  - PLoS One. 2010 Feb 25;5(2):e9432. doi: 10.1371/journal.pone.0009432.