Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of the interaction between gamma-type endorphins and the HLA class I molecules was studied by immunoelectronmicroscopy. The HLA molecules were not involved in the actual binding of endorphin to the cell. In contrast, for the endocytosis of gamma-endorphin, co-internalization of the HLA class I molecules is essential. The internalization process starts with clustering of gamma-endorphin and HLA class I molecules in coated pits. Cells that do not carry HLA class I molecules (Daudi) or do not internalize HLA class I molecules (EBV-transformed B cells) bind but do not internalize gamma-endorphin. On the basis of these observations, we suggest that the MHC class I molecules may function as transport molecules. Whether it is a general phenomenon that non-immunological ligands use the HLA class I molecules to get into the cell and immunological ligands (viral proteins) to reach the cell surface, remains to be established.
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PMID:Internalization of MHC class I molecules is a prerequisite for endocytosis of endorphin by lymphocytes. 201 8

The recognition requirements necessary for murine alloreactive cytotoxic T-cells to carry out their effector function has been investigated using target cells that express a unique class I major histocompatibility complex (MHC)-peptide pair. The human cell line T2 and the murine cell line RMA-S are defective in peptide transport components needed to effectively express stable MHC class I molecules at the cell surface. When T2 cells were infected with a vaccinia virus that encoded the Kd gene and provided with a Kd-motif peptide from the nucleoprotein of influenza virus (NPP), these cells could be lysed by polyclonal allo Kd-reactive cytotoxic T-lymphocytes (CTL). Similar results were obtained with the murine RMA-S-Kd cell line, transfected with cDNA able to express some 'empty' Kd that is heat-labile. Adding another Kd-motif peptide from influenza virus haemagglutinin (HAP) stabilized the surface expression of Kd and allowed the RMA-S-Kd cells to be lysed before or after heat shock. At 27 degrees C anti-Kd alloreactive CTL-lysed target cells in the presence and absence of HAP peptide. Alloreactive CTL appear to have a more stringent requirement for a high density of MHC class I on cell surfaces relative to peptide-specific MHC-restricted CTL. We conclude that while Kd-restricted CTL activity is strictly peptide-specific, anti-Kd-specific alloreactivity is MHC allele-specific, but peptide-nonspecific. This conclusion is at odds with the Standard Model of T-cell receptor (TCR) function, but consistent with the predictions of a Competing Model of TCR function.
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PMID:Alloreactive cytotoxic T-cell function, peptide nonspecific. 1035 67

Immune privilege in the eye is believed to originate from the eye's need to avoid the sight-destroying consequences of inflammation. Over the past 25 years, many of the anatomical, cellular, and molecular mechanisms by which the eye avoids inflammation secondary to adaptive immune responses have been elucidated. In the recent past, it has become increasingly clear that innate immune responses play a critical role in activating the adaptive immune response. Moreover, innate immunity itself carries a heavy burden of inflammation, thereby posing a threat to vision if it should occur intraocularly. Ocular immunologists have now begun to inquire into the extent to which the eye regulates the expression of innate immunity in oculi. Evidence is presented which indicates that factors found in normal aqueous humor (1) prevent NK cells from lysing their targets, (2) inhibit neutrophil activation by CD95 ligand, (3) suppress nitric oxide production by activated macrophages, and (4) interfere with complement activation via the alternative pathway. These factors include transforming growth factor-beta2, alpha-melanocyte-stimulating hormone, calcitonin gene-related peptide, and migration inhibitory factor. The ability of the eye to prevent intraocular activation of innate immune effectors spares the corneal endothelium (which expresses CD95 ligand constitutively, but low levels of MHC class I molecules) from destruction by NK cells and neutrophils, and protects the visual axis from distortion by macrophage and complement-mediated inflammation. Thus, privilege exists in the eye for both adaptive and innate immunity.
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PMID:Does innate immune privilege exist? 1077 Feb 79

This essay reviews the available evidence that the proximal hair follicle epithelium generates and maintains an area of relative immune privilege during a defined segment of the hair cycle (i.e., during anagen). This immune privilege is chiefly characterized by a very low level of expression of MHC class Ia antigens and by the local production of potent immunosuppressive agents, such as alpha-MSH and TGF-beta1. We discuss the putative functions of immune privilige of the anagen hair bulb, favoring the view that immune privilege serves mainly to sequester anagen- and/or melanogenesis-associated autoantigens from immune recognition by autoreactive CD8+ T cells. On this basis, we develop how the "immune privilege collapse model" of alopecia areata pathogenesis was conceived. In our discussion of the clinical implications of immune privilege, we outline the currently available evidence in support of this still hypothetical scenario to explain the initiation, progression, and termination of alopecia areata lesions. We review the most recent evidence from our laboratory that alpha-MSH, IGF-1, and TGF-beta1 can downregulate IFN-gamma-induced ectopic MHC class I expression in human anagen hair bulbs in vitro. Finally, we suggest that hair follicle-derived alpha-MSH, IGF-gamma, and TGF-beta1 form part of a constitutively active "IP restoration machinery" of the anagen hair bulb, which we propose to be recruited whenever the hair follicle suffers immune injury. Finally, we sketch some particularly promising avenues for future investigation into the far too long ignored hair follicle immune privilege.
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PMID:The hair follicle and immune privilege. 1458 71

The collapse of major histocompatibility complex (MHC) class-I-dependent immune privilege can lead to autoimmune disease or fetal rejection. Pragmatic and instructive models are needed to clarify the as yet obscure controls of MHC class I down-regulation in situ, to dissect the principles of immune privilege generation, maintenance, and collapse as well as to develop more effective strategies for immune privilege restoration. Here, we propose that human scalp hair follicles, which are abundantly available and easily studied, are ideally suited for this purpose: interferon-gamma induces ectopic MHC class I expression in the constitutively MHC class-I-negative hair matrix epithelium of organ-cultured anagen hair bulbs, likely via interferon regulatory factor-1, along with up-regulation of the MHC class I pathway molecules beta(2)microglobulin and transporter associated with antigen processing (TAP-2). In the first report to identify natural immunomodulators capable of down-regulating MHC class I expression in situ in a normal, neuroectoderm-derived human tissue, we show that ectopic MHC class I expression in human anagen hair bulbs can be normalized by treatment with alpha-MSH, IGF-1, or TGF-beta1, all of which are locally generated, as well as by FK506. These agents are promising candidates for immune privilege restoration and for suppressing MHC class I expression where this is clinically desired (eg, in alopecia areata, multiple sclerosis, autoimmune uveitis, mumps orchitis, and fetal or allograft rejection).
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PMID:Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model. 1474 67

Mice homozygous for the anorexia (anx) mutation are characterized by poor food intake and death by three to five weeks after birth. By P21 these mice display lower density of hypothalamic neuropeptides, including Agouti gene-related protein (AGRP). The AGRP/neuropeptide Y (NPY) system of the anx/anx mice develops normally until postnatal day (P) 12, then the normal increase in fiber density ceases, in some areas even distinctly decreases. This overlaps with activation of microglia, indicating an inflammatory and/or degenerative process. Here we studied, by in situ hybridization and immunohistochemistry (IHC), the expression of major histocompatibility complex (MHC) class I-related molecules and markers for cellular reactivity in hypothalamus of anx/anx mice. MHC class I transcript and -related proteins were found in arcuate nucleus (Arc), presumably both in neurons and glia, the latter also in areas innervated by AGRP (NPY) neurons. In the anx/anx hypothalamus, using TUNEL labeling, significantly higher number of apoptotic cells were found compared with +/+ mice, and active caspase 6 immunoreactivity was detected in degenerating NPY-fibers as well as signs of "microglia-associated cell death". In addition, Y1 receptor-labeled processes and soma of pro-opiomelanocortin (POMC) neurons, were markedly decreased at P21. These results support the hypothesis of degeneration of hypothalamic arcuate neuron populations in the anx/anx mice, whereby the AGRP system may be first affected, the changes in the POMC system being secondary in this process.
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PMID:Evidence of hypothalamic degeneration in the anorectic anx/anx mouse. 2096 82