Biomedical subjects

Hans Lassmann

Publications and source records attributed to Hans Lassmann.

At least 37 records · Page 2Linked to original sources

PubMed2005

Cortical demyelination and diffuse white matter injury in multiple sclerosis.

Focal demyelinated plaques in white matter, which are the hallmark of multiple sclerosis pathology, only partially explain the patient's clinical deficits. We thus analysed global brain pathology in multiple sclerosis, focusing on the normal-appearing white matter (NAWM) and the cortex. Autopsy tissue from 52 multiple sclerosis patients (acute, relapsing-remitting, primary and secondary progressive multiple sclerosis) and from 30 controls was analysed using quantitative morphological techniques. New and active focal inflammatory demyelinating lesions in the white matter were mainly present in patients with acute and relapsing multiple sclerosis, while diffuse injury of the NAWM and cortical demyelination were characteristic hallmarks of primary and secondary progressive multiple sclerosis. Cortical demyelination and injury of the NAWM, reflected by diffuse axonal injury with profound microglia activation, occurred on the background of a global inflammatory response in the whole brain and meninges. There was only a marginal correlation between focal lesion load in the white matter and diffuse white matter injury, or cortical pathology, respectively. Our data suggest that multiple sclerosis starts as a focal inflammatory disease of the CNS, which gives rise to circumscribed demyelinated plaques in the white matter. With chronicity, diffuse inflammation accumulates throughout the whole brain, and is associated with slowly progressive axonal injury in the NAWM and cortical demyelination.

Acute Disease↗

PubMed2005

CCR5Delta32 polymorphism effects on CCR5 expression, patterns of immunopathology and disease course in multiple sclerosis.

Four distinct patterns of tissue injury have been described in multiple sclerosis (MS) lesions. Infiltrating monocytes in lesions of all patterns co-express CCR1 and CCR5. However, in pattern II lesions, the number of CCR1 cells is decreased, while the number of CCR5 expressing cells is increased in late active versus early active regions. In contrast, CCR1 and CCR5 cells were equal in all regions of pattern III lesions. These suggest distinct inflammatory microenvironments in pattern II and III lesions and support MS pathological heterogeneity. A deletion in CCR5 (CCR5*Delta32), which encodes a truncated, non-functional protein, has been associated with late onset of MS and a favorable prognosis. We studied the association of CCR5*Delta32 with the course and severity of MS in 221 patients from a population-based cohort in Olmsted County, MN, and with patterns of immunopathology in 94 patients with biopsy-derived, pathologically confirmed demyelinating disease participating in the MS Lesion Project. The frequency of the genotypes in 221 patients from Olmsted County, MN, was 167 (75.6%) wild type, 52 (23.5%) heterozygotes, and 2 (0.9%) homozygotes. There was no association of carrier status for the CCR5*Delta32 mutation with disease severity as analyzed using the disease severity score (ranking of EDSS/duration stratified by duration), age of onset, gender or disease course (bout onset versus primary progressive). Due to low frequency of homozygotes no conclusion can be made regarding their relation to heterozygosity or wild-type status. The frequency of genotypes in the 94 biopsies was 77 (81.9%) wild type, 15 (16.0%) heterozygotes and 2 (2.1%) homozygotes. Carrier status for the CCR5*Delta32 mutation was not associated with patterns of immunopathology in MS. Despite similar numbers of T-lymphocytes, there were no CCR5+ T-cells nor was CCR5 expressed in the CNS of a homozygous CCR5*Delta32 MS patient, and heterozygous patients had reduced CCR5 expression compared to wild type patients. CCR5*Delta32 has a dose effect on CCR5 expression in the CNS, but is neither necessary for development of MS, nor CD3+ T cell recruitment into the CNS. Furthermore it does not segregate with patterns of immunopathology in MS. We did not find an association between CCR5*Delta32 mutation and disease severity and age of onset in MS.

Adult↗

PubMed2005

Combined immunostimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model.

In spite of preclinical efficacy and recent randomized, controlled studies with adenoviral vectors expressing herpes simplex virus-1 thymidine kinase (HSV1-TK) showing statistically significant increases in survival, most clinical trials using single therapies have failed to provide major therapeutic breakthroughs. Because glioma is a disease with dismal prognosis and rapid progression, it is an attractive target for gene therapy. Preclinical models using microscopic brain tumor models (e.g., < or =0.3 mm3) may not reflect the pathophysiology and progression of large human tumors. To overcome some of these limitations, we developed a syngeneic large brain tumor model. In this model, administration of single therapeutic modalities, either conditional cytotoxicity or immunostimulation, fail. However, when various immunostimulatory therapies were delivered in combination with conditional cytotoxicity (HSV1-TK), only the combined delivery of fms-like tyrosine kinase ligand (Flt3L) and HSV1-TK significantly prolonged the survival of large tumor-bearing animals (> or =80%; P < or = 0.005). When either macrophages or CD4+ cells were depleted before administration of viral therapy, TK + Flt3L therapy failed to prolong survival. Meanwhile, depletion of CD8+ cells or natural killer cells did not affect TK + Flt3L efficacy. Spinal cord of animals surviving 6 months after TK + Flt3L were evaluated for the presence of autoimmune lesions. Whereas macrophages were present within the corticospinal tract and low levels of T-cell infiltration were detected, these effects are not indicative of an overt autoimmune disorder. We propose that combined Flt3L and HSV1-TK adenoviral-mediated gene therapy may provide an effective antiglioma treatment with increased efficacy in clinical trials of glioma.

Adenoviruses, Human↗

PubMed2005

CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). It is associated with local activation of microglia and astroglia, infiltration of activated macrophages and T cells, active degradation of myelin and damage to axons and neurons. The proposed role for CX3CL1 (fractalkine) in the control of microglia activation and leukocyte infiltration places this chemokine and its receptor CX3CR1 in a potentially strategic position to control key aspects in the pathological events that are associated with development of brain lesions in MS. In this study, we examine this hypothesis by analyzing the distribution, kinetics, regulation and cellular origin of CX3CL1 and CX3CR1 mRNA expression in the CNS of rats with an experimentally induced MS-like disease, myelin oligodendrocyte glycoprotein (MOG)-induced autoimmune encephalomyelitis (EAE). METHODS: The expression of CX3CL1 and its receptor CX3CR1 was studied with in situ hybridization histochemical detection of their mRNA with radio labeled cRNA probes in combination with immunohistochemical staining of phenotypic cell markers. Both healthy rat brains and brains from rats with MOG EAE were analyzed. In defined lesional stages of MOG EAE, the number of CX3CR1 mRNA-expressing cells and the intensity of the in situ hybridization signal were determined by image analysis. Data were statistically evaluated by ANOVA, followed by Tukey\primes multiple comparison test. RESULTS: Expression of CX3CL1 mRNA was present within neuronal-like cells located throughout the neuraxis of the healthy rat. Expression of CX3CL1 remained unaltered in the CNS of rats with MOG-induced EAE, with the exception of an induced expression in astrocytes within inflammatory lesions. Notably, the brain vasculature of healthy and encephalitic animals did not exhibit signs of CX3CL1 mRNA expression. The receptor, CX3CR1, was expressed by microglial cells in all regions of the healthy brain. Induction of MOG-induced EAE was associated with a distinct accumulation of CX3CR1 mRNA expressing cells within the inflammatory brain lesions, the great majority of which stained positive for markers of the microglia-macrophage lineage. Analysis in time-staged brain lesions revealed elevated levels of CX3CR1 mRNA in microglia in the periplaque zone, as well as a dramatically enhanced accumulation of CX3CR1 expressing cells within the early-active, late-active and inactive, demyelinated lesions. CONCLUSION: Our data demonstrate constitutive and regulated expression of the chemokine CX3CL1 and its receptor CX3CR1 by neurons/astrocytes and microglia, respectively, within the normal and inflamed rat brain. Our findings propose a mechanism by which neurons and reactive astrocytes may control migration and function of the surrounding microglia. In addition, the accumulation of CX3CR1 expressing cells other than microglia within the inflammatory brain lesions indicate a possible role for CX3CL1 in controlling invasion of peripheral leucocytes to the brain.

Journal Article↗

PubMed2005

Autoimmune CD4+ T cell memory: lifelong persistence of encephalitogenic T cell clones in healthy immune repertoires.

We embedded green fluorescent CD4(+) T cells specific for myelin basic protein (MBP) (T(MBP-GFP) cells) in the immune system of syngeneic neonatal rats. These cells persisted in the animals for the entire observation period spanning >2 years without affecting the health of the hosts. They maintained a memory phenotype with low levels of L-selectin and CD45RC, but high CD44. Although persisting in low numbers (0.01-0.1% of lymph node cells) they were sufficient to raise susceptibility toward clinical autoimmune disease. Immunization with MBP in IFA induced CNS inflammation and overt clinical disease in animals carrying neonatally transferred T(MBP-GFP) cells, but not in controls. The onset of the clinical disease coincided with mass infiltration of T(MBP-GFP) cells into the CNS. In the periphery, following the amplification phase a rapid contraction of the T cell population was observed. However, elevated numbers of fully reactive T(MBP-GFP) cells remained in the peripheral immune system after acute experimental autoimmune encephalomyelitis mediating reimmunization-induced disease relapses.

Adoptive Transfer↗

PubMed2005

Cortical lesions and brain atrophy in MS.

Multiple sclerosis is generally considered a disease of the white matter. However, this is only one pathological aspect of the disease as demyelination is prominent in the grey matter of deep cerebral nuclei and the cerebral cortex. In this review, we discuss the possibility that disease involvement of grey matter structures may significantly contribute to clinical disability in multiple sclerosis patients.

Atrophy↗

PubMed2005

Stem cell and progenitor cell transplantation in multiple sclerosis: the discrepancy between neurobiological attraction and clinical feasibility.

Recent developments in our understanding of stem- and progenitor cell differentiation raises hopes that brain damage in chronic neurological diseases may become repaired by systemic or focal transplantation of such cells. In this review the potential of such an approach is discussed, but it is also highlighted that many aspects regarding its feasibility or safety are currently unresolved. Furthermore, recent findings on the pathogenesis of multiple sclerosis lesions indicate that major problems in this disease rather are related to axonal pathology and neurodegeneration rather than to the absence of oligodendrocyte progenitor cells within the lesions. In light of this complex situation, it is concluded that clinical trials of stem- or progenitor cell transplantation in multiple sclerosis are currently premature.

Animals↗

PubMed2005

Tissue preconditioning may explain concentric lesions in Baló's type of multiple sclerosis.

Lesions of Baló's concentric sclerosis are characterized by alternating layers of myelinated and demyelinated tissue. The reason for concentric demyelination in this variant of multiple sclerosis is unclear. In the present study we investigated the immunopathology in autopsy tissue of 14 patients with acute multiple sclerosis or fulminant exacerbations of chronic multiple sclerosis with Baló-type lesions in the CNS, focusing on the patterns of tissue injury in actively demyelinating lesions. We found that all active concentric lesions followed a pattern of demyelination that bears resemblances to hypoxia-like tissue injury. This was associated with high expression of inducible nitric oxide synthase in macrophages and microglia. At the edge of active lesions and, less consistently, in the outermost layer of preserved myelin, proteins involved in tissue preconditioning, such as hypoxia-inducible factor 1alpha and heat-shock protein 70, were expressed mainly in oligodendrocytes and to a lesser degree also in astrocytes and macrophages. Due to their neuroprotective effects, the rim of periplaque tissue, where these proteins are expressed, may be resistant to further damage in an expanding lesion and may therefore remain as a layer of preserved myelinated tissue.

Adolescent↗

PubMed2005

Neuropathology of CNS disease in Langerhans cell histiocytosis.

CNS involvement in Langerhans cell histiocytosis (LCH) is a rare but potentially devastating disorder. Different types of involvement have been described by MRI. CNS changes can have space-occupying or degenerative character. Little is known about the underlying neuropathology and pathophysiology. In our study we reviewed brain samples from 12 patients with LCH. The neuropathology findings were correlated with the MR morphology and the clinical presentation. By neuropathology, three types of lesions were distinguished. (i) Circumscribed granulomas within the brain's connective tissue space corresponded to tumorous lesions in the meninges or choroid plexus on MRI. They showed a composition similar to Langerhans granulomas in peripheral organs, with variable presence of CD1a-reactive cells and pronounced CD8-positive (+) T-cell infiltration. (ii) Granulomas occur within the brain's connective tissue spaces with partial infiltration of the surrounding CNS parenchyma by CD1a-reactive histiocytes. This was associated with profound T-cell-dominated inflammation and severe neurodegeneration, characterized by a nearly complete loss of neurons and axons, and gliosis. (iii) Neurodegenerative lesions lacking infiltration of CD1a+ cells, mainly affecting the cerebellum and brainstem, exhibited a profound inflammatory process dominated by CD8-reactive lymphocytes, associated with tissue degeneration, microglial activation and gliosis. Patients with such lesions showed different stages of neurological deterioration. This study indicates that neurodegeneration in LCH occurs on the background of a T-cell-dominated inflammatory process and is characterized by neuronal and axonal destruction with secondary demyelination, resembling paraneoplastic encephalitis.

Adolescent↗

PubMed2005

Complementary contribution of CD4 and CD8 T lymphocytes to T-cell infiltration of the intact and the degenerative spinal cord.

The central role of T cells in inflammatory reactions of the central nervous system (CNS) is well documented. However, there is little information about the few T cells found within the noninflamed CNS. In particular, the contribution of CD4+ and CD8+ T cells to the lymphocyte pool infiltrating the intact CNS, the location of these cells in CNS white and gray matter, and changes in the cellular composition of T-cell infiltrates coinciding with degeneration are primarily undefined. To address these points, we studied T cells in the intact and degenerative rat spinal cord. In the intact spinal cord, T cells were preferentially located within the gray matter. CD8+ T cells were more numerous than CD4+ lymphocytes. In cases of neuroaxonal degeneration or myelin degeneration/oligodendrocyte death, T cells were predominantly seen in areas of degeneration and were present in increased numbers. These effects were more pronounced for the CD4+ than for the CD8+ T-cell subset. Collectively, these data provide evidence for a clear cellular and compartmental bias in T-cell infiltration of the intact and degenerative spinal cord. This could indicate that CD4+ and CD8+ T cells might fulfill complementary roles in the intact and the diseased organ.

Aging↗

PubMed2005

Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions.

Antigen expression of a human endogenous retrovirus family, HERV-W, in normal human brain and multiple sclerosis lesions was studied by immunohistochemistry by three independent groups. The HERV-W multicopy family was identified in human DNA from the previously characterized multiple sclerosis-associated retroviral element (MSRV). A panel of antibodies against envelope (ENV) and capsid (GAG) antigens was tested. A physiological expression of GAG proteins in neuronal cells was observed in normal brain, whereas there was a striking accumulation of GAG antigen in axonal structures in demyelinated white matter from patients with MS. Prominent HERV-W GAG expression was also detected in endothelial cells of MS lesions from acute or actively demyelinating cases, a pattern not found in any control. A physiological expression of ENV proteins was detected in microglia in normal brain; however,a specific expression in macrophages was apparently restricted to early MS lesions. Thus, converging results from three groups confirm that GAG and ENV proteins encoded by the HERV-W multicopy gene family are expressed in cells of the central nervous system under normal conditions. Similar to HERV-W7q ENV (Syncitin), which is expressed in placenta and has been shown to have a physiological function in syncytio-trophoblast fusion, HERV-W GAG may thus also have a physiological function in human brain. This expression differs in MS lesions, which may either reflect differential regulation of inherited HERV-W copies, or expression of "infectious" MSRV copies. This is compatible with a pathophysiological role in MS, but also illustrates the ambivalence of such HERV antigens, which can be expressed in cell-specific patterns, under physiological or pathological conditions.

Adult↗

PubMed2005

P0(106-125) is a neuritogenic epitope of the peripheral myelin protein P0 and induces autoimmune neuritis in C57BL/6 mice.

The present study describes a new model of autoimmune neuritis in C57BL/6 mice induced by immunization with the novel neuritogenic epitope P0(106-125), derived from mouse peripheral myelin protein P0. Immunization with this peptide in combination with pertussis toxin induced high levels of peptide-specific CD4+ T cells in spleen and popliteal lymph nodes. Clinical symptoms of autoimmune neuritis started with a flaccid tail at day 10 postimmunization (p.i.), progressed to moderate paraparesis at day 15 p.i., declining thereafter with undetectable symptoms at day 40 p.i. Clinical disease activity paralleled decreased sciatic nerve motor conduction and histopathologic alterations of sciatic nerves. These included inflammatory infiltrates, mainly consisting of inducible nitric oxide synthase (iNOS)+ macrophages and CD4+ T cells. These data fit into the pathogenetic concept of murine autoimmune neuritis as a CD4+ TH1 cell-mediated disease. Our new mouse model provides an attractive tool to identify critical factors that regulate the severity of autoimmune responses in the peripheral nervous system.

Amino Acid Sequence↗

PubMed2005

Multiple sclerosis pathology: evolution of pathogenetic concepts.

This historical review describes the evolution of pathogenetic concepts of multiple sclerosis (MS) from the viewpoint of pathology. MS research is based on studies of descriptive neuropathology, performed during the 19th and early-20th century, which defined the basic nature of the inflammatory demyelinating lesions. Advances in basic immunology and neurobiology, performed during the second half of the 20th century, paved the way for the understanding of the molecular mechanims involved in inflammation and well as tissue destruction in this disease. However, recent clinical and neuroradiological studies on the evolution of the disease and its brain lesions as well as ongoing attempts to define the genetic basis of the disease indicate that our current pathogenetic concepts may be too simple and that essential aspects of MS pathology have to be redefined.

Animals↗

PubMed2004

Cellular FLIP (long isoform) overexpression in T cells drives Th2 effector responses and promotes immunoregulation in experimental autoimmune encephalomyelitis.

Cellular FLIP (c-FLIP) is an endogenous inhibitor of death receptor-induced apoptosis through the caspase 8 pathway. It is an NF-kappaB-inducible protein thought to promote the survival of T cells upon activation, and its down-regulation has been implicated in activation-induced cell death. We have generated transgenic mice overexpressing human c-FLIP long form (c-FLIP(L)) specifically in T cells using the CD2 promoter (TgFLIP(L)). TgFLIP(L) mice exhibit increased IgG1 production upon stimulation by a T cell-dependent Ag and a markedly enhanced contact hypersensitivity response to allergen. In addition to showing augmented Th2-type responses, TgFLIP(L) mice are resistant to the development of myelin oligodendrocyte glycoprotein 35-55 peptide-induced experimental autoimmune encephalomyelitis, a Th1-driven autoimmune disease. In vitro analyses revealed that T cells of TgFLIP(L) mice proliferate normally, but produce higher levels of IL-2 and show preferential maturation of Th2 cytokine-producing cells in response to antigenic stimulation. After adoptive transfer, these (Th2) cells protected wild-type recipient mice from experimental autoimmune encephalomyelitis induction. Our results show that the constitutive overexpression of c-FLIP(L) in T cells is sufficient to drive Th2 polarization of effector T cell responses and indicate that it might function as a key regulator of Th cell differentiation.

Adjuvants, Immunologic↗

PubMed2004

Steroid-responsive encephalopathy associated with autoimmune thyroiditis and primary CNS demyelination.

Steroid responsive encephalopathy associated with autoimmune thyroiditis is a well-recognized complication of autoimmune thyroid disease. However, the characterization of the histopathological features of steroid responsive encephalopathy associated with autoimmune thyroiditis are limited to six cases. Reported pathological features include vasculitis involving venules and arterioles, lymphocytic perivascular cuffs and microglial activation. We report a case of SREAT with biopsy proven (on two occasions) primary CNS demyelination and radiological evidence of steroid responsiveness, identifying primary CNS demyelination as a complication of autoimmune thyroid disease.

Adult↗

PubMed2004

Neuropathology of white matter disease in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is associated with point mutations in the mitochondrial DNA (mtDNA), coding for a mitochondrial respiratory chain complex I subunit. It is characterized by bilateral, usually sequential, optic neuropathy and may co-occur with multiple sclerosis-like white matter lesions. Despite repeated clinical reports including MRI and histopathological examination of the visual system, neuropathological descriptions of LHON associated with multiple sclerosis-like syndrome are lacking. We present here the case of a female patient with a point mutation at nucleotide position T14484C, who suffered from relapsing episodes of visual loss of both eyes and consecutively developed Hashimoto thyroiditis as well as widespread demyelinating CNS lesions outside the visual system. She died of bronchopneumonia at the age of 44 years, after a disease duration of 19 years, with progressive deterioration, epileptic seizures and immobility. Immunohistochemical analysis on formalin-fixed and paraffin-embedded tissue reveals a spectrum of neuropathological changes, including actively and inactively demyelinating plaques in the white matter and optic nerve, vacuolation and cystic necrosis with CD8-positive T cells in the frontal lobe, axonal damage, and vacuolation of white matter. Tissue destruction is associated with upregulation of mitochondrial manganese superoxide dismutase within the lesions and an increase in the expression of inducible nitric oxide synthase within macrophages and microglia. This variable phenotype of extraoptic LHON disease suggests that mtDNA mutations may affect the nervous system on a common metabolic basis and occasionally may aggravate or initiate autoimmune pathology.

Adult↗

PubMed2004

Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases.

Tumor necrosis factor (TNF) is a potent cytokine exerting critical functions in the activation and regulation of immune and inflammatory responses. Due to its pleiotropic activities, the amplitude and duration of TNF function must be tightly regulated. One of the mechanisms that may have evolved to modulate TNF function is the proteolytic cleavage of its cell surface receptors. In humans, mutations affecting shedding of the p55TNF receptor (R) have been linked with the development of the TNFR-associated periodic syndromes, disorders characterized by recurrent fever attacks and localized inflammation. Here we show that knock-in mice expressing a mutated nonsheddable p55TNFR develop Toll-like receptor-dependent innate immune hyperreactivity, which renders their immune system more efficient at controlling intracellular bacterial infections. Notably, gain of function for antibacterial host defenses ensues at the cost of disbalanced inflammatory reactions that lead to pathology. Mutant mice exhibit spontaneous hepatitis, enhanced susceptibility to endotoxic shock, exacerbated TNF-dependent arthritis, and experimental autoimmune encephalomyelitis. These results introduce a new concept for receptor shedding as a mechanism setting up thresholds of cytokine function to balance resistance and susceptibility to disease. Assessment of p55TNFR shedding may thus be of prognostic value in infectious, inflammatory, and autoimmune diseases.

Amino Acid Sequence↗

PubMed2004

The myelin-associated oligodendrocytic basic protein region MOBP15-36 encompasses the immunodominant major encephalitogenic epitope(s) for SJL/J mice and predicted epitope(s) for multiple sclerosis-associated HLA-DRB1*1501.

Autoimmune response to the myelin-associated oligodendrocytic basic protein (MOBP), a CNS-specific myelin constituent, was recently suggested to play a role in the pathogenesis of multiple sclerosis (MS). The pathogenic autoimmune response to MOBP and the associated pathology in the CNS have not yet been fully investigated. In this study, we have characterized the clinical manifestations, pathology, T cell epitope-specificity, and TCRs associated with experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with recombinant mouse MOBP (long isoform, 170 aa). Analysis of encephalitogenic MOBP-reactive T cells for reactivity to overlapping MOBP peptides defined MOBP15-36 as their major immunodominant epitope. Accordingly, MOBP15-36 was demonstrated to be the major encephalitogenic MOBP epitope for SJL/J mice, inducing severe/chronic clinical EAE associated with intense perivascular and parenchymal infiltrations, widespread demyelination, axonal loss, and remarkable optic neuritis. Molecular modeling of the interaction of I-A(s) with MOBP15-36, together with analysis of the MOBP15-36-specific T cell response to truncated peptides, suggests MOBP20-28 as the core sequence for I-A(s)-restricted recognition of the encephalitogenic region MOBP15-36. Although highly focused in their epitope specificity, the encephalitogenic MOBP-reactive T cells displayed a widespread usage of TCR Vbeta genes. These results would therefore favor epitope-directed, rather than TCR-targeted, approaches to therapy of MOBP-associated pathogenic autoimmunity. Localization by molecular modeling of a potential HLA-DRB1*1501-associated MOBP epitope within the encephalitogenic MOBP15-36 sequence suggests the potential relevance of T cell reactivity against MOBP15-36 to MS. The reactivity to MOBP15-36 detected in MS shown here and in another study further emphasizes the potential significance of this epitope for MS.

Animals↗