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Present Antigens (present + antigen)
Selected AbstractsFocal adhesion kinase mediates human leukocyte histocompatibility antigen class II-induced signaling in gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2007S. Yoshizawa Background and Objective:, The role of human leukocyte antigen class II molecules on nonantigen-presenting cells has been a matter of controversy. We previously reported that human leukocyte antigen class II molecules on human gingival fibroblasts do not present antigens, but transduce signals into the cells by making a complex with antigenic peptide T-cell receptor or by stimulating cell surface human leukocyte antigen-DR molecules with human leukocyte antigen-DR antibody (L243), which mimics the formation of the human leukocyte antigen class II,antigenic peptide T-cell receptor complex, resulting in the expression of several cytokines. The aim of this study was to detect human leukocyte antigen class II-associated molecules mediating human leukocyte antigen class II-induced signals into the cells. Material and Methods:, Antibody-based protein-microarray analysis was performed to detect activated signaling molecules in gingival fibroblasts stimulated via human leukocyte antigen class II molecules. Then, we examined if these molecules structurally associate with human leukocyte antigen class II and actually transduce signals into the cells. Results:, Stimulation of human leukocyte antigen class II on gingival fibroblasts by L243 resulted in enhanced phosphorylation of focal adhesion kinase. Focal adhesion kinase was co-immunoprecipitated with human leukocyte antigen-DR by L243. Stimulation of gingival fibroblasts with L243 induced phosphorylation of focal adhesion kinase. Luteolin, a putative focal adhesion kinase inhibitor, suppressed phosphorylation of focal adhesion kinase and dose dependently inhibited human leukocyte antigen class II-induced cytokine production. Conclusion:, Focal adhesion kinase is structurally associated with human leukocyte antigen-DR and mediates human leukocyte antigen class II-induced signals in gingival fibroblasts. [source] Pathogenic CD8+ T cells in multiple sclerosis,ANNALS OF NEUROLOGY, Issue 2 2009Manuel A. Friese MD Traditionally, autoimmune pathogeneses have been attributed to CD4+ T lymphocytes, as in multiple sclerosis (MS), rheumatoid arthritis, type 1 diabetes mellitus, and/or to B lymphocytes, as in myasthenia gravis and systemic lupus erythematosus. That is because their primary genetic associations are mostly with certain human leukocyte antigen class II alleles, whose gene products present antigens to CD4+ T cells. Because few autoimmune diseases show stronger associations with major histocompatibility complex class I alleles (ankylosing spondylitis, Behçet's disease, and psoriasis), CD8+ T cells, which interact with major histocompatibility complex class I molecules, have been largely ignored in autoimmunity research. However, a variety of findings has recently revived interest in this population, particularly in MS. First, it shows associations with major histocompatibility complex class I alleles. Second, its lesions show a predominance of CD8+ T cells. Third, these represent effectors that can directly damage central nervous system target cells. Furthermore, several clinical trials of monoclonal antibodies specifically against CD4+ T cells, or the polarizing cytokines on which they depend, have failed to show any therapeutic benefit in MS, unlike broader-spectrum antibodies that deplete all T cells. Here, we review the evidence that CD8+ T cells play a role in MS pathogenesis. Ann Neurol 2009;66:132,141 [source] Generation of self-renewing immature dendritic cells from mouse spleen that can take up mycobacteria and present antigens to T cellsAPMIS, Issue 10 2010RUBINA PAL Pal R, Marwaha S, Pepponi I, Mann JFS, Paul MJ, Reljic R. Generation of self-renewing immature dendritic cells from mouse spleen that can take up mycobacteria and present antigens to T cells. APMIS 2010; 118: 729,38. Dendritic cells (DC) play a key role in driving the adaptive immune response to Mycobacterium tuberculosis (MTB), the causative pathogen of tuberculosis (TB). However, studying these important yet very sparse immune cells in the context of MTB pathogenesis is severely restricted by the lack of suitable cell lines and the complexity of culturing of DC progenitors, usually obtained from the bone marrow. However, significant advances have been made towards generating long-term DC cultures from various lymphoid tissues. Here, we report the evidence for generating a long-term, self-renewing DC culture from the Balb/c mouse spleen. We demonstrate that these cells, termed IDC-3, have a myeloid DC origin, i.e. they are CD11c+CD11b++CD8-,,F4/80+/, and that they also display a phenotype MHC-II+CD16/32++CD80+/,CD86+, indicating that they are immature DC. Following incubation with Mycobacterium bovis BCG (Bacillus Calmette Guerin), the IDC-3 efficiently took up bacteria and acquired the morphology of mature DC. Importantly though, when IDC-3 were pre-stimulated with a mycobacterial antigen in vitro, they were able to induce proliferation of T lymphocytes from mice immunized with the same antigen. The T-cell stimulatory potential of IDC-3 was further enhanced when the cells were co-stimulated with an anti-CD40 mAb. We therefore suggest that the IDC-3 culture system could be a useful tool for studying the interaction of DC with mycobacteria. [source] | ||||||||||