Dr. Jian Han and fellow scientists at the HudsonAlpha Institute for Biotechnology were recently published with the paper—High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets—in the journal Proceedings of the National Academy of Sciences.
The human immune system includes several types of cells that defend against external threats such as bacteria, viruses and other parasites. The ability of some immune cells to remember threats the body has previously encountered is a crucial component of our immune response. These memory cells allow the immune system to activate more quickly if the threat recurs. Some of the main cells responsible for this memory, as well as other immune responses, are called T cells because they mature in the human thymus. T cells are different from other cells because they are covered with a special protein called the T cell receptor, or TCR. Because many different possible TCRs are needed to store memory of threats, human DNA encodes the potential for billions of different TCR combinations.
By uniquely combining two high-throughput genomic amplification and sequencing technologies, Han and colleagues at HudsonAlpha have produced an unprecedented view of the human “immunorepertoire,” meaning the sum of functionally diverse immune cells circulating in an individual’s immune system at a given point in time. The Han laboratory was able to determine the genomic sequences of the TCR in tens of thousands of T cells from one person’s body.
Their work has demonstrated that in a single individual, not all of the billions of possible combinations of TCR molecules are present, confirming that a process of selection has produced only certain molecules from all the possible combinations. An obvious next question is to use this technique to compare the repertoire of sequences between people, and look for correlations between the presence or absence of groups of TCR sequences and susceptibility to certain diseases.
Using the new combination of lab techniques, Han’s lab plans to examine the relationships between immune cells to uncover possible disease mechanisms associated with abnormal immunorepertoires in cancer and autoimmune diseases such as lupus and multiple sclerosis. These techniques can also be used to evaluate vaccine efficiency, identify new biomarkers and develop new therapeutics.
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