PMID- 35687696
OWN - NLM
STAT- MEDLINE
DCOM- 20220614
LR  - 20220726
IS  - 2470-9468 (Electronic)
IS  - 2470-9468 (Linking)
VI  - 7
IP  - 72
DP  - 2022 Jun 10
TI  - Clonal evolution and TCR specificity of the human T(FH) cell response to 
      Plasmodium falciparum CSP.
PG  - eabm9644
LID - 10.1126/sciimmunol.abm9644 [doi]
AB  - T follicular helper (T(FH)) cells play a crucial role in the development of 
      long-lived, high-quality B cell responses after infection and vaccination. 
      However, little is known about how antigen-specific T(FH) cells clonally evolve 
      in response to complex pathogens and what guides the targeting of different 
      epitopes. Here, we assessed the cell phenotype, clonal dynamics, and T cell 
      receptor (TCR) specificity of human circulating T(FH) (cT(FH)) cells during 
      successive malaria immunizations with radiation-attenuated Plasmodium falciparum 
      (Pf) sporozoites. Repeated parasite exposures induced a dynamic, polyclonal 
      cT(FH) response with high frequency of cells specific to a small number of 
      epitopes in Pf circumsporozoite protein (PfCSP), the primary sporozoite surface 
      protein and well-defined vaccine target. Human leukocyte antigen (HLA) 
      restrictions and differences in TCR generation probability were associated with 
      differences in the epitope targeting frequency and indicated the potential of 
      amino acids 311 to 333 in the Th2R/T* region as a T cell supertope. But most of 
      vaccine-induced anti-amino acid 311 to 333 TCRs, including convergent TCRs with 
      high sequence similarity, failed to tolerate natural polymorphisms in their 
      target peptide sequence, thus demonstrating that the T(FH) cell response was 
      limited to the vaccine strain. These data suggest that the high parasite 
      diversity in endemic areas will limit boosting of the vaccine-induced T(FH) cell 
      response by natural infections. Our findings may guide the further design of 
      PfCSP-based malaria vaccines able to induce potent T helper cell responses for 
      broad, long-lasting antibody responses.
FAU - Wahl, Ilka
AU  - Wahl I
AUID- ORCID: 0000-0002-9854-7711
AD  - Division of B Cell Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
AD  - Biosciences Faculty, University of Heidelberg, Heidelberg, Germany.
FAU - Obraztsova, Anna S
AU  - Obraztsova AS
AD  - Division of B Cell Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
AD  - Biosciences Faculty, University of Heidelberg, Heidelberg, Germany.
FAU - Puchan, Julia
AU  - Puchan J
AUID- ORCID: 0000-0003-0284-3629
AD  - Division of B Cell Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
FAU - Hundsdorfer, Rebecca
AU  - Hundsdorfer R
AUID- ORCID: 0000-0003-2482-4541
AD  - Division of B Cell Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
FAU - Chakravarty, Sumana
AU  - Chakravarty S
AUID- ORCID: 0000-0002-0426-6418
AD  - Sanaria Inc., Rockville, MD 20850, USA.
FAU - Sim, B Kim Lee
AU  - Sim BKL
AUID- ORCID: 0000-0002-8598-8905
AD  - Sanaria Inc., Rockville, MD 20850, USA.
FAU - Hoffman, Stephen L
AU  - Hoffman SL
AUID- ORCID: 0000-0002-0700-9505
AD  - Sanaria Inc., Rockville, MD 20850, USA.
FAU - Kremsner, Peter G
AU  - Kremsner PG
AUID- ORCID: 0000-0002-3926-4113
AD  - Institute of Tropical Medicine and German Center for Infection Research, 
      University of Tubingen, Tubingen, Germany.
AD  - Centre de Recherches Medicales de Lambarene, Lambarene, Gabon.
FAU - Mordmuller, Benjamin
AU  - Mordmuller B
AD  - Institute of Tropical Medicine and German Center for Infection Research, 
      University of Tubingen, Tubingen, Germany.
AD  - Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, 
      Netherlands.
FAU - Wardemann, Hedda
AU  - Wardemann H
AUID- ORCID: 0000-0003-3921-5933
AD  - Division of B Cell Immunology, German Cancer Research Center, Heidelberg, 
      Germany.
LA  - eng
GR  - R44 AI058375/AI/NIAID NIH HHS/United States
GR  - R44 AI055229/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220610
PL  - United States
TA  - Sci Immunol
JT  - Science immunology
JID - 101688624
RN  - 0 (Epitopes)
RN  - 0 (Malaria Vaccines)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Amino Acid Sequence
MH  - Clonal Evolution
MH  - Epitopes
MH  - Humans
MH  - *Malaria Vaccines
MH  - *Plasmodium falciparum
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - *T Follicular Helper Cells
EDAT- 2022/06/11 06:00
MHDA- 2022/06/15 06:00
CRDT- 2022/06/10 14:03
PHST- 2022/06/10 14:03 [entrez]
PHST- 2022/06/11 06:00 [pubmed]
PHST- 2022/06/15 06:00 [medline]
AID - 10.1126/sciimmunol.abm9644 [doi]
PST - ppublish
SO  - Sci Immunol. 2022 Jun 10;7(72):eabm9644. doi: 10.1126/sciimmunol.abm9644. Epub 
      2022 Jun 10.