MHC-restricted, glycopeptide-specific T cells show specificity for both carbohydrate and peptide residues.
(17/2670)
We examined the antigenic specificity of two T cell hybridomas elicited against the disaccharide galabiose attached to the fifth residue of the I-Ak binding peptide 52-61 of lysozyme. By making changes in the saccharide molecule and in the peptide, we conclude that the outer galactose residue of the galabiose moiety is directly recognized by the T cells together with the exposed side chains of the peptide. The overall spatial display of this galactose moiety on the 52-61 peptide is likewise important. (+info)
Inflammation alone evokes the response of a TCR-invariant mouse gamma delta T cell subset.
(18/2670)
Whether gamma delta T lymphocytes respond to microbial Ags or to inducible host Ags remains a matter of controversy. Using several different disease models and mouse strains, we and others have seen that V gamma 6/V delta 1 gamma delta T cells preferentially increase among the gamma delta T cells infiltrating inflamed tissues. However, it was not clear whether bacteria are necessary to bring about this response. Therefore, we have reexamined this question using a disease model in which inflammation is induced by a purely autoimmune process involving no bacteria, bacterial products, or other foreign material: testicular cell-induced autoimmune orchitis. Using this model we found that gamma delta T cells were still plentiful among the infiltrating T lymphocytes, being 9- to 10-fold more prevalent than in spleen, and that V gamma 6/V delta 1+ cells again represented the predominant gamma delta T cell type. This finding shows that the response of the V gamma 6/V delta 1+ subset does not, in fact, depend upon the presence of bacteria or bacterial products. The stimulus triggering the response of the V gamma 6/V delta 1 gamma delta T cells appears to be neither foreign nor organ-specific in origin, but instead consists of a self-derived host Ag or signal induced during the inflammatory process. (+info)
Presentation of antigen in immune complexes is boosted by soluble bacterial immunoglobulin binding proteins.
(19/2670)
Using a snake toxin as a proteic antigen (Ag), two murine toxin-specific monoclonal antibodies (mAbs), splenocytes, and two murine Ag-specific T cell hybridomas, we showed that soluble protein A (SpA) from Staphylococcus aureus and protein G from Streptococcus subspecies, two Ig binding proteins (IBPs), not only abolish the capacity of the mAbs to decrease Ag presentation but also increase Ag presentation 20-100-fold. Five lines of evidence suggest that this phenomenon results from binding of an IBP-Ab-Ag complex to B cells possessing IBP receptors. First, we showed that SpA is likely to boost presentation of a free mAb, suggesting that the IBP-boosted presentation of an Ag in an immune complex results from the binding of IBP to the mAb. Second, FACS analyses showed that an Ag-Ab complex is preferentially targeted by SpA to a subpopulation of splenocytes mainly composed of B cells. Third, SpA-dependent boosted presentation of an Ag-Ab complex is further enhanced when splenocytes are enriched in cells containing SpA receptors. Fourth, the boosting effect largely diminishes when splenocytes are depleted of cells containing SpA receptors. Fifth, the boosting effect occurs only when IBP simultaneously contains a Fab and an Fc binding site. Altogether, our data suggest that soluble IBPs can bridge immune complexes to APCs containing IBP receptors, raising the possibility that during an infection process by bacteria secreting these IBPs, Ag-specific T cells may activate IBP receptor-containing B cells by a mechanism of intermolecular help, thus leading to a nonspecific immune response. (+info)
Peptide dependency of alloreactive CD4+ T cell responses.
(20/2670)
Alloreactivity, the capacity of a large number of T lymphocytes to react with foreign MHC molecules, represents the cellular basis for the rejection of tissue grafts. Although it was originally assumed that the TCR of alloreactive T cells focus their recognition on the polymorphic residues that differ between the MHC molecules of responder and stimulator cells, studies in the MHC class I system have clearly demonstrated that MHC-bound peptides can influence this interaction. It remains unclear, however, whether peptides play an equally important role for the recognition of MHC class II molecules by alloreactive CD4+ T cells. Another issue that remains unresolved is the overall frequency of peptide-dependent versus peptide-independent alloreactive T cells. We have addressed these questions with antigen-presenting cells (APC) from H2-M mutant mice that predominantly express a single MHC class II-peptide complex, H2-Ab bound by a peptide (CLIP) derived from the class II-associated invariant chain. APC from these mice were used as targets and stimulators for alloreactive CD4+ T cells. Results demonstrated that the vast majority of CD4+ alloreactive T cells recognize MHC class II molecules in a peptide-dependent fashion. (+info)
Purkinje-cell-derived Sonic hedgehog regulates granule neuron precursor cell proliferation in the developing mouse cerebellum.
(21/2670)
Purkinje cells (PCs) are the projection neurons of the cerebellar cortex. They receive two major types of synaptic input - that from the inferior olive via climbing fibres and that from the granule neurons via parallel fibres. The precursors of granule neurons proliferate at the surface of the developing cerebellumin the external granule layer (EGL), which persists until postnatal day 14 in the mouse [1]. PCs are thought to provide trophic support for granule neurons [2][3] and to stimulate the proliferation of cells in the EGL [4], but the signalling molecules that mediate these cell-cell interactions have not been identified. I show here that PCs in the developing mouse cerebellum express the gene encoding the morphogen Sonic hedgehog (Shh) and that dividing cells in the EGL express Patched (Ptc) and Gli1, two target genes of which expression is upregulated in response to Hedgehog signalling (see [5] and references therein). Treatment of developing mice with hybridoma cells that secrete neutralizing anti-Shh antibodies [6] disrupted cerebellar development and reduced bromodeoxyuridine (BrdU) incorporation in the EGL of neonatal mice, whereas treatment of dissociated granule neuron cultures with recombinant Shh stimulated BrdU incorporation. These results suggest that PC-derived Shh normally promotes the proliferation of granule neuron precursors in the EGL. (+info)
The NKR-P1B gene product is an inhibitory receptor on SJL/J NK cells.
(22/2670)
The mouse NKR-P1 family includes at least three genes: NKR-P1A, -B, -C. Neither surface expression nor function of the NKR-P1B gene product has previously been shown. Here, we demonstrate that the SJL/J allele of the NKR-P1B gene product is expressed on SJL/J NK cells, and is recognized by PK136 mAb. Interestingly, the same mAb does not recognize the NKR-P1B gene product of C57BL/6. We have also generated a novel mAb, 1C10, that recognizes an activation receptor on SJL/J NK cells. Activation of the NKR-P1B receptor-inhibited 1C10 mAb induced redirected lysis and recruited SHP-1, indicating that NKR-P1B is an inhibitory receptor. Therefore, the mouse NKR-P1 gene family, like the Ly49 family, includes both activation and inhibitory receptors. (+info)
Tumour necrosis factor and interferon-gamma are required in host resistance against virulent Rhodococcus equi infection in mice: cytokine production depends on the virulence levels of R. equi.
(23/2670)
Rhodococcus equi is a facultative intracellular bacterial pathogen that causes pneumonia in foals and immunosuppressed humans. There are at least three virulence levels of R. equi and these pathogenicities are associated, in mice, with the presence of virulence plasmids. This study focused on cytokine secretion, in mice, in the course of a primary infection with sublethal doses of R. equi strains of different virulence levels (virulent, intermediately virulent and avirulent). Tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma), but not interleukin-4 (IL-4) and interleukin-10 (IL-10), were induced endogenously in mice in relation to the multiplication and clearance of virulent and intermediately virulent strains of R. equi. These cytokines were not detected in mice infected with avirulent R. equi. Deaths occurred among mice treated with monoclonal antibodies (mAbs) against either TNF or IFN-gamma prior to sublethal dose infection with virulent and intermediately virulent strains of R. equi, but not with avirulent R. equi. These results suggested that cytokine production depended largely on the virulence levels of R. equi: TNF and IFN-gamma were required early during infection with virulent R. equi to limit replication and clearance of bacteria within the organs, but they were not necessary for limiting infection with avirulent R. equi. (+info)
CD147 monoclonal antibodies induce homotypic cell aggregation of monocytic cell line U937 via LFA-1/ICAM-1 pathway.
(24/2670)
CD147 is a 50 000-60 000 MW glycoprotein of the immunoglobulin superfamily broadly expressed on haemopoietic cell lines and peripheral blood cells. In the present study, six monoclonal antibodies (mAbs) directed against the CD147 protein were generated. The antigen defined by the generated CD147 mAbs is widely expressed on haemopoietic cell lines, peripheral blood cells and is a lymphocyte activation-associated cell surface molecule. The generated CD147 mAbs precipitated a broad protein band from U937 cells of 45 000-65 000 MW under reducing conditions. Functional analysis indicated that the CD147 mAbs markedly induced homotypic cell aggregation of U937 cells, but not K562 cells. The CD147 mAb-induced cell aggregation was inhibited by leucocyte function-antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) mAbs. However, the expression of LFA-1 and ICAM-1 molecules on U937 was not altered by CD147 mAb treatment. The U937 cell aggregation induced by CD147 mAb was also inhibited by ethylenediamine tetra-acetic acid (EDTA), sodium azide and when incubated at 4 degrees. We therefore propose that the binding of CD147 mAb to CD147 molecule, which mimics the natural ligand binding, may generate intracellular signals that activate LFA-1/ICAM-1 intercellular adhesion pathway. (+info)