We recently discover a new immune escape mechanism that may help viruses escape from immune detection, which might compromise vaccine efficacy. Viruses that cause chronic infection in human contain higher numbers of T cell epitopes whose TCR-facing amino acids are identical to those of numerous peptides from the human proteome. We postulate that viruses that incorporate such human-like epitopes may exploit host tolerance to avoid or suppress effector responses. In order to predict these human-like epitopes, we developed an immunoinformatics tool, JanusMatrix.
Using JanusMatrix, we have identified T cell epitopes in H7N9 influenza HA protein that are highly conserved with human genome epitopes, and these epitopes possess low immunogenicity, activate natural Tregs and suppress bystander effector T cell responses in vitro. The human like T cell epitopes may contribute to the delayed, low titer of H7N9 hemagglutination inhibiting antibody responses and diminished seroconversion rates that have been observed in human infections and unadjuvanted H7 HA vaccination clinical trials. We also turned our attention to HIV-1 and found several such epitopes in the envelope (Env) protein of HIV-1, one of which was included in both the HIV-1 E and HIV-1 B Env antigens that were used in the ‘moderately effective’ HIV RV144 trial in Thailand. Validation of the immunological role of these epitopes is in the process.