Structural Basis for Clonal Diversity of the Public T Cell Response to Dominant Epitopes from Cytomegalovirus and Influenza

A diverse T cell receptor (TCR) repertoire is a prerequisite for effective viral clearance. However, knowledge of human TCR repertoire to defined viral antigens is limited. Recent advances in high-throughput sequencing (HTS) and single-cell sorting have revolutionized the study of human TCR repertoires to different types of viruses. In collaboration with the laboratory of Dr. Nan-ping Weng (National Institute on Aging, NIH), we applied unique molecular identifier (UMI)-labelled HTS, single-cell paired TCR analysis, surface plasmon resonance, and X-ray crystallography to exhaustively interrogate CD8+ TCR repertoires specific for cytomegalovirus (CMV) and influenza A (Flu) in HLA-A2+ humans. Our two CMV-specific TCR-pMHC structures and two Flu-specific TCR-pMHC structures provide a plausible explanation for the much higher diversity of CMV-specific than Flu-specific TCR repertoires in humans. Our comprehensive biochemical and structural portrait of two different anti-viral T cell responses may contribute to the future development of predictors of immunity or disease at the individual level.

ATTACHMENT, GROWTH AND PERSISTENCE OF CRONOBACTER ON GRANULAR ACTIVATED CARBON FILTERS

Several Cronobacter outbreaks have implicated contaminated drinking water. This study assessed the impact of granular activated carbon (GAC) on the microbial quality of the water produced. A simulated water filter system was installed by filling plastic columns with sterile GAC, followed by sterile water with a dilute nutrient flowing through the column at a steady rate. Carbon columns were inoculated with Cronobacter on the surface, and the effluent monitored for Cronobacter levels. During a second phase, commercial faucet filters were distributed to households for 4-month use. Used filters were backwashed with sterile peptone water, and analyzed for Cronobacter, total aerobic plate count, coliform bacteria and Enterobacteriaceae. Cronobacter colonized the simulated GAC and grew when provided minimal levels of nutrients. Backwashed used filters used in home settings yielded presumptive Escherichia coli, Pseudomonas and other waterborne bacteria. Presumptive Cronobacter strains were identified as negative through biochemical and genetic test.