The authors chose to look at individuals with HLA type A24, a type that is relatively common in Japanese and some populations in other countries, including several Asian countries.

Fujii made this choice because it was easy to find individuals with this HLA type, as others are much less common. They felt it might offer insights into why some populations in Asia have appeared to be less susceptible to the infections.

The group began using in silico analysis to look for parts of the SARS-CoV-2 spike protein that can bind highly with HLA-A24. As a result, they identified six potential epitopes—sequences of amino acids that immune cells respond to.

They then looked at the reaction of peripheral immune cells in people with the HLA-A24 type who had not been infected with SARS-CoV-2 to see whether they had memory killer T cells that would respond to antigens from the virus.

Around 80 percent uninfected healthy donors with the A24 type HLA did show a reaction for a single peptide—a sequence they called the QYI epitope—which they identified.

Finally, they found that QYI-specific memory killer T cells from donors with the A24 serotype showed cross-reactivity against the relevant epitopes, which are relatively conserved from human coronaviruses, including seasonal coronaviruses.

The group then looked at the response in patients with blood cancers, who are particularly susceptible to serious COVID-19. The response was much smaller than those from non-exposed healthy individuals.

Importantly, however, the group discovered that even in patients with blood cancers, there is a “hotspot” located in the spike protein of the virus—a sequence of 27 amino acids around the QYI epitope—and that T cells responding to this can still mount a vigorous immune response.

One hundred percent of healthy people and 65 percent of blood cancer patients responded for the hotspot. According to Fujii, “This leads to the hope of developing vaccines that could boost the immune response even in immunocompromised patients.

Source: Medindia