Library

Notes: Summary: The class I major histocompatibility complex (MHC class 1) presents 8–10 residue peptides to cytotoxic T lymphocytes. Most of these antigenic peptides are generated during protein degradation in the cytoplasm and are then transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP), Several lines of evidence have indicated that the proteasome is the major proteolytic activity responsible for generation of antigenic peptides—probably most conclusive has been the finding that specific inhibitors of die proteasome block antigen presentation. However, other proteases (e.g. the signal peptidase) may also generate some epitopes, particularly those on certain MHC class I alleles. The proteasome is responsible for generating the precise C termini of many presented peptides, and appears to be the only activity in ceils that can make this cleavage. In contrast, aminopeptidases in the cytoplasm and endoplasmic reticulum can trim the N terminus of extended peptides to their proper size. Interestingly, the cellular content of proteases involved in the production and destruction of antigenic peptides is modified by inter-feron-γ (IFN-γ) treatment of cells, IFN-γ indicates the expression of three new proteasome β submits that are preferentially incorporated into new proteasomes and alter their pattern of peptidase activities. These changes are likely to enhance the yield of peptides with C termini appropriate for MHC binding and have been shown to enhance the presentation of at least some antigens. IFN-γ also upregulates leucine aminopeptidase, which should promote the removal of N-terminal flanking residues of antigenic peptides. Also, this cytokine downregulates the expression of a metallo-proteinase, thimet oligopeptidase that actively destroys many antigenic peptides. Thus, IFN-γ appears to increase the supply of peptides by stimulating their generation and decreasing their destruction. The specificity and content of these various proteases should determine the amount of peptides available for antigen presentation. Also, the efficiency with which a peptide is presented is determined by the protein's half life (e.g. its ubiquitination rate) and the sequences flanking antigenic peptides, which influence the rates of proteolytic cleavage and destruction.

Notes: Background:  Antigen-loaded eosinophils instilled intratracheally into mice were capable of migrating into local lymph nodes and localize to the T cell-rich paracortical zones where they stimulated antigen-specific proliferation of CD4+ T cells. The aim of the present study was to evaluate whether eosinophils within the tracheobronchial lumen can stimulate Th2 cell expansion by presenting antigen both in vitro and in vivo.Methods:  Airway eosinophils were recovered from ovalbumin-sensitized and -challenged BALB/c mice, these eosinophils were then co-cultured with sensitized CD4+ cells in the absence or presence of anti-CD80 or/and -CD86 monoclonal antibodies. Airway eosinophils were instilled into the trachea of sensitized mice. At 3 days thereafter, the draining paratracheal lymph nodes were removed and teased into cell suspensions for culture. Cell-free culture supernatants were collected for detection of cytokines.Results:  Our data showed that airway eosinophils functioned as CD80- and CD86-dependent antigen-presenting cells (APCs) to stimulate sensitized CD4+ lymphocytes to produce interleukin (IL)-4, IL-5, and IL-13, but not interferon (IFN)-γ in in vitro assay. When instilled intratracheally in sensitized recipient mice, airway eosinophils migrated into draining paratracheal lymph nodes primed Th2 cells in vivo for IL-4, IL-5, and IL-13, but not IFN-γ, production during the in vitro culture that was also CD80- and CD86-dependent.Conclusion:  Eosinophils within the lumina of airways could process inhaled antigen function in vitro and in vivo as APCs to promote expansion of Th2 cells. This investigation highlights the potential of eosinophils to not only act as terminal effector cells but also to actively modulate immune responses by amplifying Th2 cell responses.