Human memory T cell responses to microbes: specificity and function

Researchers:

Federico Mele, PhD Student

Status: In progress

Memory T and B cells represent a repository of the antigenic experience of the individual. Heterogeneity is a hallmark of memory T cells (Figure). Defining the distribution of antigen-specific memory cells in different memory compartments can provide useful information on the in vivo response following infection or vaccination. We are performing a systematic analysis of the frequency, distribution, and fine specificity of T cells specific for different microbes in naïve, effector and memory T cell subsets. To study the antigenic repertoire of memory T cell subsets, Th1, Th2, Th17, Th22 and other memory T cell subsets are isolated from peripheral blood according to expression of CD45RO and chemokine receptors. T cell libraries from these subsets are generated and interrogated simultaneously for reactivity against a panel of antigens from viruses (e.g. CMV, HBV, Influenza virus), bacteria (e.g. Mycobacterium tuberculosis, Staphylococcus aureus) and fungi (e.g. Candida albicans). Since different classes of molecules are involved in the presentation of microbial antigens to CD4⁺ T cells, namely MHC-II (for peptide antigens) and CD1-family (for lipid antigens), we will perform the screening using either monocytes (MHC class II⁺CD1a^–CD1b^–CD1c^–) or monocyte-derived DCs (MHC class II⁺CD1a⁺CD1b⁺CD1c⁺, Sallusto, 1994) in order to study the distribution of T cells specific for protein or lipid antigens (Barral and Brenner, 2007). Antigen-specific T cell clones are isolated from responding T cell lines and tested for their fine specificity (using recombinant proteins and overlapping peptide libraries) and for their capacity to produce cytokines, in particular IFN-γ, IL-4, IL-5, IL-13, IL-17, IL-22, and IL-10. We expect to gain important information on the distribution, frequency and class of the human T cell response to different pathogens and in different stimulatory conditions (natural infection or vaccination).

T cell-mediated immune responses: heterogeneity and specialization. Differentiation signal(s), transcription (TX) factor usage, effector molecule(s), homing receptors, target cells and function of each T cell subset.