myelin-basic-protein and Autolysis

Cytotoxic T cells reactive with myelin basic protein (MBP) may be isolated from most human subjects. Since activated T cells express major histocompatibility complex (MHC) class II antigens, we assessed whether MBP-specific, CD4+ T cells could present MBP or synthetic MBP peptides to themselves and whether this provoked self lysis. We examined two MBP-specific cell lines and eight T cell clones recognizing four different MBP epitopes. All T cell populations presented MBP as well as synthetic peptides to themselves eliciting self lysis of the T cell clones. CD4+ T cell populations recognizing another central nervous system (CNS) protein, proteolipid protein (PLP), or the recall antigen, Candida, did not exhibit this antigen-induced, autocytolytic activity. However, activated, PLP-reactive T cells were susceptible to lysis by cytotoxic MBP-specific T cells in the presence of MBP. These results suggest that antigen-induced self lysis of activated human T cells might limit an autoimmune response within a target organ independent of other immunoregulatory mechanisms.

Topics: Autoantigens; Autolysis; Cell Line, Transformed; Clone Cells; Electrophoresis, Polyacrylamide Gel; Epitopes; Humans; Myelin Basic Protein; Myelin Proteins; Myelin Proteolipid Protein; T-Lymphocytes; Time Factors

To study the distribution of myelin-associated glycoprotein (MAG) in human nervous tissue and in multiple sclerosis (MS) lesions, we used paraffin sections and our modification of the peroxidase-antiperoxidase technique. Sections of MS lesions also were treated with antiserum to basic protein (BP) and with histological stains for axons and myelin sheaths. In tissue from normal developing central nervous system, oligodendroglia, their processes, and wwly formed myelin sheaths were intensely stained by MAG antiserum. In adults, MAG was found in periaxonal regions of myelinated fibers of the central and peripheral nervous system. The most striking finding in MS lesions was the extension of decreased MAG immunostaining into white matter that appeared normal when treated with BP antiserum or luxol fast blue. In acute early MS lesions the decrease in MAG immunostaining extended far beyond the margin of acute demyelination, where the BP staining of degenerating sheaths often was increased. In chronic inactive plaques, this decrease in periaxonal MAG immunostaining was limited to relatively few fibers in a thin rim around each lesion. These observations suggest that in MS, immunoreactivity of periaxonal MAG is altered before myelin breakdown begins. Early in degeneration, myelin sheaths and their fragments often were more intensely stained by BP antiserum than normal sheaths; later the staining intensity decreased. In shadow plaques, BP antiserum stained some oligodendroglia. Their appearance and location among thinly myelinated axons suggested that these oligondendroglia were forming new sheaths around previously demyelinated axons.

Topics: Acute Disease; Adolescent; Adult; Aged; Animals; Autolysis; Central Nervous System; Child; Child, Preschool; Chronic Disease; Glycoproteins; Histological Techniques; Humans; Immunoenzyme Techniques; Infant; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Rats; Staining and Labeling

Myelin basic protein in normal mice is phosphorylated. Since phosphorylation can decrease the net positive charge of the myelin basic protein, this could affect molecular interactions between this protein and other myelin components. In this study 32P incorporation into small and large components of the myelin basic protein was studied in immature and young adult mice and also in Quaking mutants which have a severe myelin deficit. We found a short half-life of 32P in myelin basic protein. The 32P specific activity of myelin basic protein was higher in immature and Quaking mice than in young adult animals. Of the 32P-labeled basic proteins of control and Quaking mice, the small component had a slightly higher specific activity than the large component. Although the small basic protein is quantitatively decreased in Quaking mice, the ratio of specific activity of small to large basic protein is similar in control and Quaking animals. Since Quaking and immature mice have many uncompacted myelin lamellae, these preliminary results suggest that phosphorylation and dephosphorylation could be involved in compaction mechanisms.

Topics: Aging; Animals; Autolysis; Brain; Mice; Mice, Quaking; Myelin Basic Protein; Myelin Sheath; Phosphates; Phosphorylation

Topics: Animals; Autolysis; Brain; Brain Edema; Central Nervous System; Demyelinating Diseases; Edema; Female; Lipid Metabolism; Myelin Basic Protein; Myelin Proteins; Myelin Sheath; Rats; Spinal Cord; Spinal Cord Diseases; Time Factors; Triethyltin Compounds

Topics: Animals; Autolysis; Brain Chemistry; Cattle; Electrophoresis, Polyacrylamide Gel; Freezing; Myelin Basic Protein; Myelin Sheath; Nerve Tissue Proteins; Occipital Lobe