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The immune response to SARS-CoV-2 may be restricted by a set of genes

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Neutralizing antibody Although onset within 2 weeks of SARS-CoV-2 infection, its durability and intensity can vary from individual to individual, raising concerns about long-term immune prospects. Effectiveness of COVID 19 vaccine.

In a PLOS ONE paper published online February 11, 2021, researchers at the University of California, San Diego Medical School found that individual immune responses to SARS-CoV-2, the virus that causes COVID-19, are key tissue-matching genes. It reports that it may be limited by. A complex or set of variable genes encoding MHC, a cell surface protein essential for the adaptive immune system.

Specifically, senior authors Maurizio Zanetti, MD, and Hannah Carter, MD, and colleagues investigated how MHC interacts with two types of lymphocytes or immune cells called T and B. It was.

The immune system responds to invading pathogens by producing antibodies aimed at blocking and neutralizing the pathogens.The production of antibodies to a protein requires productive cooperation between T and B lymphocytes, both of which must recognize their adjacencies. antigen A sequence initiated by MHC on B cells. Adjacent peptide sequences are preferentially and non-randomly involved in the two cells. MHC acts as a link between T and B lymphocytes in this process. “

Dr. Maurizio Zanetti, Professor of Medicine, University of California, San Diego

Based on this reasoning, researchers have found that all possible fragments of the pedromer RBM, which triggers both human immune response and vaccine activity, are associated with over 5,000 different MHC molecules present in the world’s population. Was analyzed by computer.

Surprisingly, the authors found that MHC had a low average tendency to display RBD-derived peptides. Since MHC binding is an indirect measure of the probability that T cells will be activated and stimulate B lymphocytes to produce antibodies against RBM, the authors found that the production of RBM-specific antibodies was a virus to MHC. These parts of.

“This can reduce the neutralizing antibody response,” said Andrea Castro, the lead author who is a member of Carter’s lab. “And in the case of SARS-CoV-2, inadequate presentation of major RBD fragments by many MHC alleles can interfere with the production of neutralizing antibodies that target RBM.”

Scientists suggest that an individual’s immunological history may play a role in the activation of B lymphocytes capable of producing T cell responses and subsequent strongly targeted neutralizing antibodies. I will.

According to Carter, there are two potential impacts of this study.

“One is that the ability to produce antibodies with strong neutralizing activity can vary considerably from individual to individual in the general population, reflecting the great genetic diversity of MHC. Lifespan where the lack of effective cooperation between T and B lymphocytes neutralizes the antibody response of infected people. “

The authors state that studies have reported that neutralizing antibodies in infected individuals (inpatients, health care workers, convalescents) are reduced within 3 months.

“We may add to these considerations the effects of newly discovered mutations in RBM, such as viral variants in the United Kingdom, South Africa and Brazil,” said Zanetti. The mutational topology of these new variants represents a further potential disruption of immunological relay between T and B lymphocytes, which is a high-quality, long-lived neutralizing antibody for individuals in the world population. It further adversely affects the ability to generate a response. SARS-CoV-2. “

Source:

Journal reference:

Castro, A. , et al. (2021) In silico analysis suggests less effective MHC-II presentation of SARS-CoV-2 RBM peptide: effect on neutralizing antibody response. PLOS ONE. doi.org/10.1371/journal.pone.0246731..

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