Recombinant antibodies derived from laser captured single plasma cells of multiple sclerosis brain identified phage peptides which may be used as tools for characterizing intrathecal IgG response
| Autor: | Tiffany Pointon, Michael W. Graner, Deandra Walker, Anthony Fringuello, Peter G. E. Kennedy, Xiaoli Yu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Multiple Sclerosis Phage display Plasma Cells Immunology Peptide Laser Capture Microdissection CD38 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid Antigen medicine Humans Immunology and Allergy Bacteriophages Amino Acid Sequence Panning (camera) Injections Spinal Laser capture microdissection chemistry.chemical_classification Multiple sclerosis Brain medicine.disease Molecular biology Peptide Fragments Recombinant Proteins 030104 developmental biology Neurology chemistry Immunoglobulin G Neurology (clinical) 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroimmunology. 347:577319 |
| ISSN: | 0165-5728 |
| DOI: | 10.1016/j.jneuroim.2020.577319 |
| Popis: | Oligoclonal bands and increased IgG antibody levels can be detected in the cerebrospinal fluid in vast majority of patients with Multiple Sclerosis (MS). However, the antigenic specificity of oligoclonal IgG has yet to be determined. Using laser capture microdissection, we isolated single CD38+ plasma cells from lesion areas in two autopsy MS brains, and generated three recombinant antibodies (rAbs) from clonally expanded plasma cells. Panning phage-displayed random peptide libraries was carried out to determine peptide antigen specificities of these MS brain rAbs. We identified 25 high affinity phage peptides from which 5 peptides are unique. Database searches revealed that they shared sequence homologies with Epstein-Barr nuclear antigens 4 and 6, as well as with other viral proteins. Significantly, these peptides were recognized by intrathecal IgG and oligoclonal IgG bands in other MS patients. Our results demonstrate that functional recombinant antibodies can be generated from clonally expanded plasma cells in MS brain lesions by laser capture microdissection, and that these MS brain rAbs have the potential for determining the targets of intrathecal IgG and oligoclonal bands. |
| Databáze: | OpenAIRE |
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