scholarly journals Mannan-MOG35-55 Reverses Experimental Autoimmune Encephalomyelitis, Inducing a Peripheral Type 2 Myeloid Response, Reducing CNS Inflammation, and Preserving Axons in Spinal Cord Lesions

2020 ◽  
Vol 11 ◽  
Author(s):  
Anastasia Dagkonaki ◽  
Maria Avloniti ◽  
Maria Evangelidou ◽  
Irini Papazian ◽  
Ioannis Kanistras ◽  
...  
Keyword(s):  
Spinal Cord ◽  
T Cell ◽  
Mhc Class Ii ◽  
Clinical Symptoms ◽  
Neuronal Damage ◽  
Class Ii ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Peripheral Type

CNS autoantigens conjugated to oxidized mannan (OM) induce antigen-specific T cell tolerance and protect mice against autoimmune encephalomyelitis (EAE). To investigate whether OM-peptides treat EAE initiated by human MHC class II molecules, we administered OM-conjugated murine myelin oligodendrocyte glycoprotein peptide 35-55 (OM-MOG) to humanized HLA-DR2b transgenic mice (DR2b.Ab°), which are susceptible to MOG-EAE. OM-MOG protected DR2b.Ab° mice against MOG-EAE by both prophylactic and therapeutic applications. OM-MOG reversed clinical symptoms, reduced spinal cord inflammation, demyelination, and neuronal damage in DR2b.Ab° mice, while preserving axons within lesions and inducing the expression of genes associated with myelin (Mbp) and neuron (Snap25) recovery in B6 mice. OM-MOG-induced tolerance was peptide-specific, not affecting PLP178-191-induced EAE or polyclonal T cell proliferation responses. OM-MOG-induced immune tolerance involved rapid induction of PD-L1- and IL-10-producing myeloid cells, increased expression of Chi3l3 (Ym1) in secondary lymphoid organs and characteristics of anergy in MOG-specific CD4+ T cells. The results show that OM-MOG treats MOG-EAE in a peptide-specific manner, across mouse/human MHC class II barriers, through induction of a peripheral type 2 myeloid cell response and T cell anergy, and suggest that OM-peptides might be useful for suppressing antigen-specific CD4+ T cell responses in the context of human autoimmune CNS demyelination.

scholarly journals A polyalanine peptide with only five native myelin basic protein residues induces autoimmune encephalomyelitis.

1992 ◽  
Vol 176 (2) ◽  
pp. 605-609 ◽  
Author(s):  
A M Gautam ◽  
C I Pearson ◽  
D E Smilek ◽  
L Steinman ◽  
H O McDevitt
Keyword(s):  
T Cell ◽  
Myelin Basic Protein ◽  
Mhc Class Ii ◽  
Basic Protein ◽  
Class Ii ◽  
Autoimmune Encephalomyelitis ◽  
T Cell Stimulation ◽  
Disease Induction ◽  
Mhc Class Ii Molecules

The minimum structural requirements for peptide interactions with major histocompatibility complex (MHC) class II molecules and with T cell receptors (TCRs) were examined. In this report we show that substituting alanines at all but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not alter its ability to bind A alpha uA beta u (MHC class II molecules), to stimulate specific T cells and, surprisingly, to induce experimental autoimmune encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice. Most other amino acid side chains in the Ac1-11 peptide are essentially irrelevant for T cell stimulation and for disease induction. Further analysis revealed that binding to A alpha uA beta u occurred with a peptide that consists mainly of alanines and only three of the original residues of Ac1-11. Moreover, when used as a coimmunogen with MBP Ac1-11, this peptide inhibited EAE. The finding that a specific in vivo response can be generated by a peptide containing only five native residues provides evidence that disease-inducing TCRs recognize only a very short sequence of the MHC-bound peptide.

Decreased expression of MHC class II and cathepsin E in dendritic cells might contribute to impaired induction of antigen-specific T cell response in NC/Nga mice

2012 ◽  
Vol 59 (1,2) ◽  
pp. 95-101 ◽  
Author(s):  
Tohru Sakai ◽  
Emi Shuto ◽  
Tomoyo Taki ◽  
Honami Imamura ◽  
Miku Kioka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cell Response ◽  
Class Ii ◽  
T Cell Response ◽  
Cathepsin E

T-cell Epitope-based Vaccine Design for Nipah Virus by Reverse Vaccinology Approach

2020 ◽  
Vol 23 (8) ◽  
pp. 788-796
Author(s):  
Praveen K.P. Krishnamoorthy ◽  
Sekar Subasree ◽  
Udhayachandran Arthi ◽  
Mohammad Mobashir ◽  
Chirag Gowda ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Vaccine Development ◽  
Nipah Virus ◽  
3D Structure ◽  
Cell Epitope ◽  
Class Ii ◽  
Class I ◽  
Reverse Vaccinology ◽  
Stable Complex

Aim and Objective: Nipah virus (NiV) is a zoonotic virus of the paramyxovirus family that sporadically breaks out from livestock and spreads in humans through breathing resulting in an indication of encephalitis syndrome. In the current study, T cell epitopes with the NiV W protein antigens were predicted. Materials and Methods: Modelling of unavailable 3D structure of W protein followed by docking studies of respective Human MHC - class I and MHC - class II alleles predicted was carried out for the highest binding rates. In the computational analysis, epitopes were assessed for immunogenicity, conservation, and toxicity analysis. T – cell-based vaccine development against NiV was screened for eight epitopes of Indian - Asian origin. Results: Two epitopes, SPVIAEHYY and LVNDGLNII, have been screened and selected for further docking study based on toxicity and conservancy analyses. These epitopes showed a significant score of -1.19 kcal/mol and 0.15 kcal/mol with HLA- B*35:03 and HLA- DRB1 * 07:03, respectively by using allele - Class I and Class II from AutoDock. These two peptides predicted by the reverse vaccinology approach are likely to induce immune response mediated by T – cells. Conclusion: Simulation using GROMACS has revealed that LVNDGLNII epitope forms a more stable complex with HLA molecule and will be useful in developing the epitope-based Nipah virus vaccine.

scholarly journals Analysis of T-cell hybridomas with an unusual MHC class II-dependent ligand specificity

Immunology ◽  
1996 ◽  
Vol 89 (2) ◽  
pp. 238-244 ◽  
Author(s):  
S. K. MENDIRATTA ◽  
N. SINGH ◽  
V. BAL ◽  
S. Rath
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Ligand Specificity
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