T Cell Self/Foreign Recognition Mechanism Discovered

Researchers led by Howard Hughes Medical Institute investigator K. Christopher Garcia have established how the structure of receptors on the surface of T cells enables this dual recognition, a phenomenon known as alloreactivity. Garcia and his colleagues found that T-cell receptors that adeptly recognize foreign or self antigen-displaying molecules can do so using highly divergent structural solutions. The study was published in the journal Cell.

Garcia and his colleagues set out to analyze how the structure of a specific type of T-cell receptor changed depending on whether it was grabbing onto a self or foreign MHC molecule. “These structures, as well as other experiments we did, showed that the T-cell receptor uses a completely different recognition mechanism for the foreign and self MHC-protein complex,” said Garcia. “Instead of recognizing the similarities, it actually recognizes the differences between them. This was a huge surprise, and it has significant implications for understanding the co-evolution of genes for T-cell receptors and for MHC proteins,” he said.

The immune system’s rejection of transplanted organs has been difficult to explain from an evolutionary perspective, according to Garcia. “Transplantation from person to person is not something that human biology could have ever anticipated,” he said. Better understanding of the fundamental underpinnings of the immune system could help in developing new ways to prevent transplant rejection by damping alloreactivity, he said.

Source: HHMI News