Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we reported that expression of the murine beta 2-microglobulinb (beta 2mb) antigenic epitopes defined by the mAb S19.8 and 23 (SJL [beta 2ma] anti-B10.S beta 2mb]) was dependent upon association of beta 2m with MHC class I heavy chains. We have further explored the antigenic properties of beta 2m under circumstances requiring the induction of MHC class I surface expression with heavy chain-specific peptide-ligand. For the RMA-S cell line, which is class I surface null due to a defect in the TAP-2 peptide transporter, treatment with the H-2Kb-specific vesicular stomatitis virus-derived N p52-59 peptide resulted in the cell surface expression of the epitopes defined by the anti-H-2Kb mAb Y-3, as well as equally strong expression of the epitopes defined by the anti-beta 2mb mAb S19.8 and 23. Similarly, the FLU-NP p366-374 peptide induced H-2Db on the surface of RMA-S cells as determined by cytofluorometry with the mAb MKQ8; however, expression of the epitope defined by S19.8 was only partially recovered and no reactivity was observed for mAb 23. That the H-2Db heavy chain was assembled with beta 2mb on the cell surface was established from immunoprecipitation experiments with 125I-surface-radiolabeled RMA-S cells treated with FLU-NP p366-374; MKQ8 immunoprecipitated prominent heavy chain and beta 2m bands, whereas S19.8 and 23 isolated a weak beta 2m band (12-15% of that co-immunoprecipitated with MKQ8). These results are consistent with the observation that human beta 2m-deficient cells (designated FO-1) transfected with the B2mb allele were induced, in combination with the endogenous HLA class I heavy chains, to express the epitope defined by S19.8, but not mAb 23, whereas both were expressed when contransfection was performed with the H-2Kb gene. That the determinants recognized by S19.8 and 23 were formed by a discontinuous cluster of amino acids within beta 2m was established from experiments demonstrating that H-2Kb heavy chain assembled with a chimeric beta 2m molecule (comprising human beta 2m from 1-69 and mouse beta 2m from amino acid 70-99, including the polymorphic residue Ala 85) did not lead to expression of the S19.8 and 23 epitopes. The results of this study provide evidence that heavy chain polymorphism can affect the antigenic properties of beta 2m and offer insight into the basis by which CTL may react against beta 2mb when assembled with the H-2Kb molecule.
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PMID:MHC class I heavy chain-dependent expression of discontinuous antigenic epitopes on beta 2-microglobulinb is inducible with peptide-ligand. 753 Aug 67

A C164Y somatic mutation in the H-2Kb class I molecule causes a disruption of the alpha 2 domain disulfide bond and results in a loss of H-2Kb cell surface expression by the 69.9.15 cell line. In vitro culture of the somatic cell variant at 30 degrees C induced weak, but reproducible, expression of the H-2Kb mutant molecule on the cell surface, which suggests that a temperature-sensitive mutation was contributing to the H-2Kb null phenotype. Based on the inherent structural instability of the mutant H-2Kb molecules synthesized by 69.9.15 cells, we sought to determine the ability of high affinity peptide-ligand to counteract the null expression of H-2Kb. Treatment of 69.9.15 cells was performed with acid-eluted cell-derived peptides, as well as synthetic H-2Kb-restricted peptides, ovalbumin (OVA) p257-264 (YSIINFEKL), and vesicular stomatitis virus-nuclear protein p52-59 (RGYVYQGL). Whereas the endogenous and vesicular stomatitis virus peptides were ineffective at inducing H-2Kb expression at either 37 degrees C or 30 degrees C, treatment with the OVA peptide at 30 degrees C gave rise to dose-dependent enhancement in H-2Kb expression, an effect that was independent of exogenous sources of bovine beta 2-microglobulin at the time of peptide treatment. By comparison, expression of H-2Kb remained unaltered when cells were treated with the OVA peptide at 37 degrees C, consistent with the temperature-sensitive expression of the mutant molecules. Decay of H-2Kb from the cell surface was similar for both 69.9.15 and RMA-S cells, an indication that binding of OVA p257-264 provided the same level of stability for class I molecules with either a cis-(69.9.15) or trans-acting (RMA-S) defect in heavy chain transport. These data provide novel evidence that transport-defective MHC class I molecules, similar in nature to those encoded by class I genes isolated from human genomic libraries, i.e., the 12.4 pseudogene with a polymorphism at amino acid position 164 (C-->F), are subject to high affinity peptide-induced stabilization which reverses the class I null phenotype.
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PMID:Failure in expression of structurally altered (CYS164-->TYR) H-2Kb molecules is mitigated with high affinity peptide-ligand. 776 72

Two major nuclear factor-kappaB (NF-kappaB) signalling pathways are involved in the regulation of the immune response. While the classical NF-kappaB pathway is responsible for regulation of genes encoding components of the innate immune response, the alternative NF-kappaB signalling pathway mediates processes of the adaptive immune system. To evaluate the role of the NF-kappaB signalling pathways in the control of viral infection, we have used lymphocytic choriomeningitis virus (LCMV) infection of mice, which is known to be an excellent model for studying antiviral immune responses. Via the use of mice that were deficient in NF-kappaB subunits from either the classical (p50(-/-) mice) or the alternative NF-kappaB pathway (p52(-/-) mice), we were able to demonstrate that the alternative NF-kappaB pathway is required for the T-cell-mediated immune response against LCMV. Mice that were deficient in the alternative NF-kappaB pathway subunit p52 showed an impaired T-cell response against LCMV infection. Furthermore, these mice also showed an impaired T-cell-dependent humoral immune response against vesicular stomatitis virus (VSV) infection. Adoptive transfer experiments revealed that impaired priming, but not the T-cell response itself, was responsible for the defective cellular immune response against LCMV infection. Our data demonstrate that a functional alternative NF-kappaB signalling pathway is required to assure an adequate immune response after viral infection.
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PMID:The alternative NF-kappaB signalling pathway is a prerequisite for an appropriate immune response against lymphocytic choriomeningitis virus infection. 2056 93