Immunodominance in CD4 T Cell Responses
In specific immune responses pathogens or to protein antigens, T lymphocytes only respond to a limited number of peptide epitopes from the immunogens. These peptides are termed immunodominant. Our experiments seek to understand the elements in vivo that dictate the narrowed selection of specificities in CD4 T cells during protective immune response, particularly pathogens such as influenza virus. One of our long-term goals is to apply the knowledge gained in animal models towards human vaccine design.
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The Role of DM in Selecting Epitopes for CD4 T Cell Responses
The MHC-encoded DM molecule is a critical component of the class II presentation pathway and catalyzes peptide loading onto class II molecules by binding to the class II protein and stabilizing a conformation that promotes peptide exchange. Early studies on endogenous antigen presentation by MHC class II molecules by our laboratory and other laboratories were the first that suggested that DM functions as a peptide exchange protein and can act as either a positive or negative regulator of the cell surface expression peptides:class II complexes and thus the ability of these complexes to recruit and promote expansion of the CD4 T cells.
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Peptide Persistence on Class II Provides a Competitive Advantage to T Cells During Priming and Expansion In Vivo
Recent findings describing the dynamic interactions of antigen-bearing dendritic cells and T cells suggested to us that peptide off-rates from class II molecules may impact the immune outcome at several levels, after the initial expression at the cell surface. To explore this issue, we evaluated whether CD4 T cell responses were impacted by the ability of class II peptide complexes to persist after export to the cell surface.
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The Specificity and Role of CD4 T Cells During the Response to Influenza Viruses and Vaccines
The emergence of a pandemic influenza virus in Mexico in 2009, like other viruses with pandemic potential of earlier years has prompted great interest in understanding the nature of immunological memory to influenza, and whether and how previous encounters with influenza virus and vaccines influence our ability to mount a protective immune response when confronting relatively novel strains of this virus.
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The Specificity and Function of Follicular CD4 T Cells in Response to Protein Vaccination and Influenza Infection
The production of high affinity, isotype switched antibodies in response to vaccines or pathogens depends on B cell interaction with antigen-specific CD4 T cells in the germinal centers of the peripheral lymphoid organs. It is now known that this activity is mediated by a specialized subset of CD4 T cells termed follicular helper T cells (Tfh) that are characterized by the expression of a subset of cell surface markers that promote the ability of the CD4 T cells to help B cells and to localize to the B cell follicles and participate in the germinal center reaction.
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