Daniel A. Achinko
Howard University,USA.
Title: Genetic Regulation of Lymphocyte-Specific Proto-Oncogene (LCK), Differentially Selects The Right MHC Class I Variants Against a Disease
Biography
Biography: Daniel A. Achinko
Abstract
LCK gene known as lymphocyte-specific proto-oncogene, is associated with coordinated expression of Major Histocompatibility Complexes (MHC), class I and II T-Lymphocytes, in response to physiological stimuli, mediated through a combined interaction of promoters, suppressors and enhancers. Proximal and distal promoters, functioning independently and developmentally regulated, favor proper LCK transcription. The former is thymocyte related while the latter involves all stages of T-cell development. LCK is genetically and functionally associated with several diseases including HIV and EBOLA, serious threats to human existence. LCK driven immune selection research for therapeutic intervention derives little scientific interest.
The last Ebola outbreak (2014), emerging from Guinee, and expanding to Liberia, Sierra Leone, Nigeria and USA, pushed the scientific community to find an urgent therapy against the disease. Our work focused on looking at HLA class I & II subtypes expressed after the Ebola virus (EBOV) attack with focus on the most potent related antigenic epitopes generating favorable immune response to eliminate the disease. LCK dominantly observed in genetic interaction analysis was associated with T-cell antigen receptor (TCR)-linked signal transduction pathways hence differentially selecting for CD4 (MHC II) and CD8 (MHC I) immune variants.
Data obtained from Gene Omnibus database at NCBI, showed two LCK related disease clusters, grouping EBOV with different cancer types and a down regulation of most CD8 immunogenic variants (HLA A, B, C) compared to CD4 variants. This MHC expression pattern, suggests a careful regulatory pattern for LCK and related expression of T-cell immune variants whose antigenic specificity is key to resolving the disease burden. We are currently using modern genetic technology to engineer the right LCK variants required to drive downstream expression of the required MHC class I immune variants for a specific pathogen, which could be further designed for therapeutic applications against Ebola and related diseases