The specific γδ TCR repertoire in response to malaria

The prospect of overcoming deadly diseases, such as malaria, requires a greater understanding of how our immune system responds to the causative agent. There is still much to learn and discover about our complicated immune system; however, our knowledge has exponentially improved thanks to next-generation sequencing (NGS). To determine the immune response to Plasmodium falciparum malaria, Dr. Martin Davey’s team analyzed the T cell receptor (TCR) repertoire, specifically the repertoire of γδ T cells, using iRepertoire’s human TCRδ and TCRγ iR-Profile Kits.¹ Here we will discuss his lab’s recently published findings.

Impact of malaria infection γδ T cell profiles

Adults and children living in locations with high malaria transmission have distinct γδ T cell profiles. While investigating Malian children over 3 malaria seasons with high P. falciparum transmission, it was found that the Vδ1 effector γδ T cell population expanded after episodes of febrile malaria. This then begs the question of whether episodes of febrile malaria alter individual γδ T cell clonotypes over time.

Comparing the γδ TCR repertoires of Malian children versus Australian children

The analysis of the γδ T cell populations was divided into two groups: Vγ9/Vγ2⁺ (Vγ2⁺) and non-Vγ9/Vγ2 (Vγ2^neg) populations. Malian and Australian children had a similar Vγ2⁺ population but differed in the Vγ2^neg T cell population. Additionally, the Malian children had increased levels of CD27^lo CX₃CR1⁺ effector cells, while Australian children had more CD27^hiCX₃CR1^neg naïve cells. Furthermore, the Vγ2^neg γδ TCR repertoire among Malian children had increased clonotype expansion while exhibiting decreased clonotype diversity and shared sequences. As a result, this may suggest a role of malaria exposure in altering the Vγ2^neg γδ T cell population.

Alteration of the Vγ2^neg γδ TCR repertoire by malaria infection

The Vγ2^negγδ TCR repertoire was altered after an incidence of acute febrile malaria. Further analysis of the CD27^lo CX₃CR1⁺ Vδ1 effector cells demonstrated an impact of febrile malaria on clonotype frequency and diversity. This was further supported in vivo in an adult model for controlled human malaria infection. Repeated infection led to remodeling of the Vγ2^negγδ TCR repertoire as characterized by increased differentiation of Vδ1 effector cells. It was also observed that previous malaria infections would prime these cells for proliferation.

In summary, Dr. Davey and colleagues characterized the γδ TCR repertoire in response to P. falciparum infection with the help of iRepertoire’s arm-PCR technology. The immune response consisted of an innate-like Vγ2⁺ response followed by clonal expansion of select Vδ1 effector T cells. Further characterization of the γδ TCR repertoire will not only improve our understanding of the acquired immunity against malaria but will also help inform us on how to improve disease management.

Read the full study here: https://www.science.org/doi/10.1126/scitranslmed.abe7430

References

1. Borstel, A. von et al. Repeated Plasmodium falciparum infection in humans drives the clonal expansion of an adaptive γδ T cell repertoire. Sci. Transl. Med. 13, 7430 (2021).