T cell response to myelin basic protein in the context of the multiple sclerosis-associated HLA-DR15 haplotype: peptide binding, immunodominance and effector functions of T cells.

Abstract:

:In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131-159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.

journal_name

J Neuroimmunol

authors

Vergelli M,Kalbus M,Rojo SC,Hemmer B,Kalbacher H,Tranquill L,Beck H,McFarland HF,De Mars R,Long EO,Martin R

doi

10.1016/s0165-5728(97)00075-1

subject

Has Abstract

pub_date

1997-08-01 00:00:00

pages

195-203

issue

2

eissn

0165-5728

issn

1872-8421

pii

S0165-5728(97)00075-1

journal_volume

77

pub_type

杂志文章
  • TLR-2 neutralization potentiates microglial M1 to M2 switching by the combinatorial treatment of ciprofloxacin and dexamethasone during S. aureus infection.

    abstract::Microglial inflammation plays a pivotal role in the pathogenesis of S. aureus induced brain abscesses. The objective of this study was to regulate microglial activation by the combinatorial treatment of ciprofloxacin either with dexamethasone or celecoxib via targeting M1 and M2 polarization. The antibiotic-immunomodu...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2020.577262

    authors: Dey R,Bishayi B

    更新日期:2020-07-15 00:00:00

  • Additive effects of combination treatment with anti-inflammatory and neuroprotective agents in experimental autoimmune encephalomyelitis.

    abstract::We studied the effects of combination treatment with an anti-inflammatory agent, interferon (IFN)-beta, and a putative neuroprotective agent, an estrogen receptor (ER)-beta ligand, during EAE. Combination treatment significantly attenuated EAE disease severity, preserved axonal densities in spinal cord, and reduced CN...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2009.11.018

    authors: Du S,Sandoval F,Trinh P,Voskuhl RR

    更新日期:2010-02-26 00:00:00

  • Total glucosides of peony attenuates experimental autoimmune encephalomyelitis in C57BL/6 mice.

    abstract::Total glucosides of peony (TGP), an active compound extracted from the roots of Paeonia lactiflora Pall, has wide pharmacological effects on nervous system. Here we examined the effects of TGP on experimental autoimmune encephalomyelitis (EAE), an established model of multiple sclerosis (MS). The results showed that T...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2015.05.009

    authors: Huang Q,Ma X,Zhu DL,Chen L,Jiang Y,Zhou L,Cen L,Pi R,Chen X

    更新日期:2015-07-15 00:00:00

  • Human immunodeficiency virus type-1 Nef protein induces blood-brain barrier disruption in the rat: role of matrix metalloproteinase-9.

    abstract::We recently showed that MMP-9 activity was detectable in the cerebrospinal fluid (CSF) of about half of neurologically symptomatic HIV-infected patients. Using an experimental animal model, we detected MMP-9 activity in CSF samples from rats that had been injected intracisternally with recombinant HIV-1 Nef protein, b...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/s0165-5728(99)00170-8

    authors: Sporer B,Koedel U,Paul R,Kohleisen B,Erfle V,Fontana A,Pfister HW

    更新日期:2000-01-24 00:00:00

  • Parental genes do not codominantly confer susceptibility to experimental autoimmune encephalomyelitis in F1 rats.

    abstract::Lewis (LEW) and DA rats are highly susceptible to experimental autoimmune encephalomyelitis (EAE) induced with guinea pig myelin basic protein (MBP), but respond to different epitopes. The dominant epitope for LEW rats is MBP73-86, and disease is mediated primarily by Vbeta8.2 Th1 cells. DA rats lack conventional Vbet...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/s0165-5728(01)00244-2

    authors: Lenz DC,Wolf NA,Swanborg RH

    更新日期:2001-03-01 00:00:00

  • Th17 expansion in MS patients is counterbalanced by an expanded CD39+ regulatory T cell population during remission but not during relapse.

    abstract::In this study, percentages of CD39(+) Treg and Th17 cells were compared between relapsing-remitting MS patients and controls and were related to the vitamin D status. The Th17 cell population was expanded in about 40% of the MS patients. In MS patients in remission, but not during relapse, a positive association was f...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2011.09.013

    authors: Peelen E,Damoiseaux J,Smolders J,Knippenberg S,Menheere P,Tervaert JW,Hupperts R,Thewissen M

    更新日期:2011-12-15 00:00:00

  • A pilot test of pioglitazone as an add-on in patients with relapsing remitting multiple sclerosis.

    abstract::The peroxisome proliferator-activated receptor gamma agonist pioglitazone is FDA-approved for treatment of type-2 diabetes due to insulin sensitizing effects. However pioglitazone has anti-inflammatory and neuroprotective effects, reduces glial and T-cell activation, and reduces signs in an animal model of multiple sc...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.jneuroim.2009.04.011

    authors: Kaiser CC,Shukla DK,Stebbins GT,Skias DD,Jeffery DR,Stefoski D,Katsamakis G,Feinstein DL

    更新日期:2009-06-25 00:00:00

  • Guillain-Barré syndrome with IgM antibody to the ganglioside GalNAc-GD1a.

    abstract::We analyzed the characteristics of 29 Guillain-Barré syndrome (GBS) patients with IgM anti-GalNAc-GD1a antibodies. Fourteen of them had had an antecedent cytomegalovirus infection (CMV group) and 12 gastrointestinal infection (G-I group). Most of the G-I group patients (nine of 12) were subsequent to Campylobacter jej...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/s0165-5728(00)00451-3

    authors: Kaida K,Kusunoki S,Kamakura K,Motoyoshi K,Kanazawa I

    更新日期:2001-02-15 00:00:00

  • Glial activation and midkine and pleiotrophin transcription in the ventral tegmental area are modulated by morphine administration.

    abstract::Opiates cause persistent restructuring in the mesolimbic reward system. Although a possible role for midkine and pleiotrophin cytokines in the field of synaptic plasticity has been proposed, it has not been assessed whether morphine administration regulates astrogliosis and midkine and pleiotrophin transcription. We o...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2014.07.017

    authors: García-Pérez D,Luisa Laorden M,Núñez C,Victoria Milanés M

    更新日期:2014-09-15 00:00:00

  • Suppression of experimental autoimmune encephalomyelitis by gallium nitrate.

    abstract::We examined the effect of gallium (Ga) nitrate on the development of the development of experimental autoimmune encephalomyelitis (EAE). Weekly subcutaneous injections of 10-30 mg/kg prevented clinical signs as well as histopathological changes of EAE. The optimal timing of a single injection of Ga was 6 days after in...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/0165-5728(92)90186-o

    authors: Whitacre C,Apseloff G,Cox K,Matkovic V,Jewell S,Gerber N

    更新日期:1992-07-01 00:00:00

  • Differential effects on glial activation by a direct versus an indirect thrombin inhibitor.

    abstract::Thrombin is a potent regulator of brain function in health and disease, modulating glial activation and brain inflammation. Thrombin inhibitors, several of which are in clinical use as anti-coagulants, can reduce thrombin-dependent neuroinflammation in pathological conditions. However, their effects in a healthy CNS a...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2016.05.018

    authors: Marangoni MN,Braun D,Situ A,Moyano AL,Kalinin S,Polak P,Givogri MI,Feinstein DL

    更新日期:2016-08-15 00:00:00

  • Intravenous immunoglobulin reduces β amyloid and abnormal tau formation caused by herpes simplex virus type 1.

    abstract::Intravenous immunoglobulin (IVIG) treatment of Alzheimer's disease (AD) has been encouraging. Its mechanism of action might be via anti-β-amyloid (Aβ) antibodies which facilitate Aβ clearance. However, IVIG's benefits might result from its antiviral activity, particularly against herpes simplex virus type 1 (HSV1), a ...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2013.01.005

    authors: Wozniak MA,Itzhaki RF

    更新日期:2013-04-15 00:00:00

  • Pancreatic ductal cell antigens are important in the development of invasive insulitis in Non-Obese Diabetic mice.

    abstract::Type 1 Diabetes (T1D) is an autoimmune disease in which insulin producing beta cells of the pancreas are selectively destroyed. Glial Fibrillary Acidic Protein (GFAP) expressed in peri-islet Schwann cells (pSCs) and in the ductal cells of the pancreas is one of the candidate autoantigens for T1D. Immune responses to G...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2019.01.001

    authors: Jayasimhan A,Ellis DP,Ziegler AI,Slattery RM

    更新日期:2019-02-15 00:00:00

  • Methylene blue alleviates experimental autoimmune encephalomyelitis by modulating AMPK/SIRT1 signaling pathway and Th17/Treg immune response.

    abstract::Methylene blue (MB) is an effective neuroprotectant in many neurological disorders. AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1 (SIRT1) plays a crucial role in maintaining inflammatory responses and shows a synergistic effect on cell homeostasis. We investigated the effect...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2016.08.014

    authors: Wang J,Zhao C,Kong P,Bian G,Sun Z,Sun Y,Guo L,Li B

    更新日期:2016-10-15 00:00:00

  • Studies on terminal deoxynucleotidyl transferase and adenosine deaminase in myasthenic thymus.

    abstract::Thymic function in myasthenic patients was examined using two biochemical markers which specifically define a population of cortisone-sensitive cortical thymocytes. The enzymatic activities of terminal deoxynucleotidyl transferase (TdT) and adenosine deaminase (ADA) were determined in 13 samples. High contents of both...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/0165-5728(84)90067-5

    authors: Vezzoni P,Fiacchino F,Clerici L,Sghirlanzoni A,Cerrato D,Peluchetti D,Lucchini R,Raineri M,Cornelio F

    更新日期:1984-09-01 00:00:00

  • Increased serum levels of soluble CD14 indicate stable multiple sclerosis.

    abstract::The aim of this study was to evaluate a possible role of soluble CD14 (sCD14) in multiple sclerosis (MS). We found that sCD14 serum levels measured by ELISA were higher in MS patients compared to neurological and healthy controls. Within the MS group sCD14 levels were increased in relapsing-remitting and secondary pro...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2006.09.002

    authors: Lutterotti A,Kuenz B,Gredler V,Khalil M,Ehling R,Gneiss C,Egg R,Deisenhammer F,Berger T,Reindl M

    更新日期:2006-12-01 00:00:00

  • Monocytes in active multiple sclerosis: intact regulation of HLA-DR density in vitro despite decreased HLA-DR density in vivo.

    abstract::HLA-DR expression on circulating monocytes varies as a function of disease activity in patients with multiple sclerosis (MS), a putative immunopathological demyelinating disorder. Specifically, monocytes isolated from subjects with active MS exhibit reduced HLA-DR antigen density, and immunoregulatory aberrations such...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/0165-5728(92)90001-2

    authors: Ransohoff RM,Tuohy VK,Barna BP,Rudick RA

    更新日期:1992-04-01 00:00:00

  • Inhibition of AGEs/RAGE/Rho/ROCK pathway suppresses non-specific neuroinflammation by regulating BV2 microglial M1/M2 polarization through the NF-κB pathway.

    abstract::The microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Advanced glycation end products (AGEs)/receptor for advanced glycation end products (RAGE) or Rho/Rho kinase (ROCK) are both involved in the development of non-specific inflammation. However, there are few...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2017.02.010

    authors: Chen J,Sun Z,Jin M,Tu Y,Wang S,Yang X,Chen Q,Zhang X,Han Y,Pi R

    更新日期:2017-04-15 00:00:00

  • Interstrain variability of autoimmune encephalomyelitis in rats: multiple encephalitogenic myelin basic protein epitopes for DA rats.

    abstract::We investigated T cell epitopes of guinea pig myelin basic protein (MBP) that induce experimental autoimmune encephalomyelitis (EAE) in DA rats, using synthetic peptides that correspond to regions of the guinea pig MBP molecule that are homologous to rat MBP. Four peptides were encephalitogenic when tested in DA rats....

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/s0165-5728(97)00084-2

    authors: Stepaniak JA,Wolf NA,Sun D,Swanborg RH

    更新日期:1997-09-01 00:00:00

  • A novel protective model against experimental allergic encephalomyelitis in mice expressing a transgenic TCR-specific for myelin oligodendrocyte glycoprotein.

    abstract::Myelin oligodendrocyte glycoprotein (MOG) is an important autoantigen in multiple sclerosis and in experimental autoimmune encephalomyelitis (EAE). We generated a T cell receptor (TCR) transgenic (Tg) mouse expressing a TCR derived from an encephalitogenic T cell clone specific for MOG(35-55). This mouse failed to dev...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2003.12.007

    authors: Mendel I,Natarajan K,Ben-Nun A,Shevach EM

    更新日期:2004-04-01 00:00:00

  • Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

    abstract::Programmed death-1 (PD-1) belongs to the CD28 family of co-stimulatory and co-inhibitory molecules and regulates adaptive immunity. This molecule induces the development of regulatory T cells, T cell tolerance, or apoptosis. We examined the role of PD-1 pathway in Theiler's murine encephalomyelitis virus (TMEV)-induce...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2014.06.018

    authors: Takizawa S,Kaneyama T,Tsugane S,Takeichi N,Yanagisawa S,Ichikawa M,Yagita H,Kim BS,Koh CS

    更新日期:2014-09-15 00:00:00

  • Caveolin-3 is aberrantly expressed in skeletal muscle cells in myasthenia gravis.

    abstract::Caveolin-3 is a muscle-specific membrane protein that localizes to the sarcolemma and T-tubule system. Caveolin-3 is needed for muscle repair and skeletal muscle development. The objective of this study was to compare caveolin-3 expression in myasthenia gravis (MG) and control muscles. Caveolin-3 was abnormally expres...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2016.10.011

    authors: Iwasa K,Furukawa Y,Yoshikawa H,Yamada M

    更新日期:2016-12-15 00:00:00

  • Enhanced glial activation and expression of specific CNS inflammation-related molecules in aged versus young rats following cortical stab injury.

    abstract::Aging is associated with increased glial responsiveness that may enhance the brain's susceptibility to injury and disease. To determine whether unique age-related molecular responses occur in brain injury, we assessed mRNA levels of representative central nervous system (CNS) inflammation-related molecules in young (3...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/s0165-5728(01)00404-0

    authors: Kyrkanides S,O'Banion MK,Whiteley PE,Daeschner JC,Olschowka JA

    更新日期:2001-10-01 00:00:00

  • TGF-β1/Smad2/3/Foxp3 signaling is required for chronic stress-induced immune suppression.

    abstract::Depending on the duration and severity, psychological tension and physical stress can enhance or suppress the immune system in both humans and animals. Although it has been established that chronic stress exerts a significant suppressive effect on immune function, the mechanisms by which affects immune responses remai...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2017.11.005

    authors: Zhang H,Caudle Y,Wheeler C,Zhou Y,Stuart C,Yao B,Yin D

    更新日期:2018-01-15 00:00:00

  • T lymphocyte subset abnormalities in peripheral blood from patients with the Guillain-Barré syndrome.

    abstract::T lymphocytes are probably of pathogenic importance in many autoimmune diseases. Recently, deviations of circulating T-helper (CD4+) subpopulations have been noticed. Blood samples from 12 patients with Guillain-Barré syndrome (GBS) were studied with flow cytometry during their disease course to define circulating T c...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/0165-5728(94)90032-9

    authors: Dahle C,Vrethem M,Ernerudh J

    更新日期:1994-09-01 00:00:00

  • Lymphocyte responsiveness to lectin and myelin antigens in canine distemper infection in relation to the development of demyelinating lesions.

    abstract::Eleven dogs were experimentally infected with canine distemper virus and studied for periods of up to 63 days post-inoculation. The responsiveness of lymphocytes in vitro toward phytohemagglutinin, myelin basic protein and galactocerebroside was tested at regular intervals during the course of infection by means of [3...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/0165-5728(83)90013-9

    authors: Cerruti-Sola S,Kristensen F,Vandevelde M,Bichsel P,Kihm U

    更新日期:1983-04-01 00:00:00

  • Transforming growth factor-beta 1 inhibits tumor necrosis factor-alpha/lymphotoxin production and adoptive transfer of disease by effector cells of autoimmune encephalomyelitis.

    abstract::We previously reported that the CD4+ suppressor cells (Ts) that regulate recovery of Lewis rats from experimental autoimmune encephalomyelitis (EAE) produce transforming growth factor-beta (TGF-beta). We also reported that TGF-beta downregulates interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2) production, by...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/0165-5728(94)90131-7

    authors: Stevens DB,Gould KE,Swanborg RH

    更新日期:1994-04-01 00:00:00

  • Sequential polymicrobial infections lead to CNS inflammatory disease: possible involvement of bystander activation in heterologous immunity.

    abstract::VV(PLP) is a recombinant vaccinia virus (VV) encoding myelin proteolipid protein (PLP) that has been used to investigate molecular mimicry and autoimmunity. Since virus infections can cause bystander activation, mice were first infected with VV(PLP), and later challenged with wild-type VV, lymphocytic choriomeningitis...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2007.05.012

    authors: Tsunoda I,Libbey JE,Fujinami RS

    更新日期:2007-08-01 00:00:00

  • Sex hormone-dependent attenuation of EAE in a transgenic mouse with astrocytic expression of the RNA regulator HuR.

    abstract::In experimental autoimmune encephalomyelitis (EAE) and other neurodegenerative diseases, astrocytes play an important role in promoting or attenuating the inflammatory response through induction of different cytokines and growth factors. HuR plays a major role in regulating many of these factors by modulating RNA stab...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2012.02.014

    authors: Wheeler C,Nabors LB,Barnum S,Yang X,Hu X,Schoeb TR,Chen D,Ardelt AA,King PH

    更新日期:2012-05-15 00:00:00

  • Fetal thymus graft prevents age-related hearing loss and up regulation of the IL-1 receptor type II gene in CD4(+) T cells.

    abstract::We found that rejuvenation of the recipient immunity by inoculation of young CD4(+) T cells or a fetal thymus graft led to down regulation of the interleukin 1 receptor type II (IL-1R2) gene in CD4(+) T cells and reduced age-related hearing loss and degeneration of the spiral ganglion in SAMP1 mice, a murine model of ...

    journal_title:Journal of neuroimmunology

    pub_type: 杂志文章

    doi:10.1016/j.jneuroim.2012.05.007

    authors: Iwai H,Inaba M

    更新日期:2012-09-15 00:00:00