Helper T cells that drive antibody formation, no ‘cross-reaction’ between clones
T-cell receptor binds only antigenic determinants present in vaccines
German Center for Cancer Research, paper in ‘Science Immunology’
More than 600,000 malaria deaths occur each year in Africa, Southeast Asia, South America and the Middle East.
Malaria is a type of parasitic disease caused by the bite of a mosquito and infecting the malaria parasite.
The pathogen, the protozoan malaria, is a unicellular eukaryote that is completely different from bacteria or viruses.
Five types of malaria parasites are known, but the most dangerous is the ‘tropical parasite’, abbreviated Pf (Plasmodium falciparum).
In Korea, only one species of ‘P. vivax’ is found, but it is rare that the basic treatment works well and death is rare.
In places like southeast Africa, where it is most affected, malaria is almost endemic.
However, the residents of this area, where malaria infection is common, are also re-infected when a new mutant protozoa appears.
This means that so-called ‘cross-immunity’ hardly works.
German scientists have figured out why this is happening.
The ‘helper T cells’ involved in ‘immune memory’ failed to induce a broad immune response against the malaria parasite.
The results of this study conducted by scientists at the German Cancer Research Center (DKFZ) were published in the journal Science Immunology on the 10th (local time).
When an experimental vaccine is made from dead Pf sporozoites and administered, an immune response is produced that suppresses infection of these sporozoites when bitten by mosquitoes.
The DKFZ research team wanted to find out which protein sequence in the malaria vaccine responds to helper T cells.
Vaccines are designed to target a protein called CSP.
The malaria parasite infects humans at the sporozoite stage. Among the proteins that appear on the surface of these sporozoites, CSP is the most abundant.
To improve a malaria vaccine, it is first necessary to know which protective antibodies are produced by the immune response.
However, antibodies are produced depending on follicular helper T cells.
To transform B cells into plasma cells (antibody-producing cells) or memory B cells, the help of these helper T cells is essential.
The research team isolated dead Pf sporozoites from the vaccine and injected them into volunteers. Volunteers were selected from European descent who had never contracted malaria.
Then, ‘Pf-identifying’ follicular helper T cells induced in the body were analyzed at the single-cell level.
Here are surprising results.
The helper T-cell receptors target mainly two amino acids (311 and 333) of the CSP protein.
Also, there was no ‘cross-reactivity’ between different T cell clones.
“The helper T-cell receptor precisely bound to the epitope of CSP, which was originally present in the vaccine,” said Heda Bardemann, associate professor of immunology, the corresponding author of the paper. explained.
This suggests a high level of ‘sequence polymorphism’ in the two amino acid regions of the CSP protein in the naturally occurring parasite.
This stringency when the helper T cell receptor binds to the epitope of the malaria protozoa prevents the immune system from being generated by natural infection, the team pointed out.
This is the reason why Africans do not develop immunity even though they are always exposed to malaria infection, and that vaccines do not work for long even if they are vaccinated.
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2022/06/20 18:00 Send