We will carry out deep sequencing of rearranged immunoglobulin (Ig) and T cell receptor (TCR) genes from lymphocytes in human subjects responding to several distinct viral (H1N1 influenza, varicella zoster, and measles/mumps/rubella) and bacterial (meningococcal) vaccines, as well as natural infections with HI N1 influenza and varicella zoster. Our initial analysis will examine rearranged Ig and TCR repertoire in total peripheral blood lymphocyte populations. Subsequent analysis will define repertoire in subsets of Bcells and T-cells selected on the basis of their immunophenotype or antigen binding activity. These data will provide a fine-detailed view of the number, size, and receptor sequence features of expanded B and T cell clones arising during these human immune responses, and will be correlated with a variety of parallel serological and cellular functional immune assays from the Stanford Human Immune Monitoring Research (SHIMR) Center to enable detection ofthe characteristics of effective vaccination and the immune response to natural infection. The effects of patient age and genetic bacl We will apply new DNA sequencing methods to study the unique receptors expressed by populations of B and T cells in the immune system following protective vaccination against viral and bacterial diseases, and during active infections. Better understanding of which B cells and T cells respond to vaccination and infection, and which are most helpful for fighting disease, will aid the design and testing of new vaccines.Public Health Relevance
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