Antigenic determinants of T lymphocyte alpha beta receptor and other leukocyte surface proteins as differential markers of skeletal muscle regeneration: detection of spatially and timely restricted patterns by MAM microscopy.
Different stages of human muscle regeneration have been identified by multiple antigen-mapping (MAM) microscopy at the level of a novel marker system. This immunofluorescence method allows the selective imaging of numerous antigen signals from cells or tissue sections. It is shown that 2 monoclonal antibodies (mAbs) against the common region of the alpha beta T lymphocyte antigen receptor (alpha beta and alpha TCR chains) and 3 mAbs against the leukocyte surface antigens Leu8, OKM5 and Leu19 recognize regenerating muscle cells at different time points of regeneration in human muscle sections. Paradoxically, these epitopes are not expressed by T lymphocytes or other mononuclear leukocytes invading regenerating muscle. Hence, presence of the corresponding antigens in muscle fibers may exclude their expression by muscle-invasive immune cells suggesting a function in muscle-specific cell-to-cell recognition. Simultaneous localization of these epitopes in Duchenne dystrophy reveals 10 different phenotypes of regenerating and normal infantile muscle cells due to different developmental stages during the myocyte differentiation. In adult muscle (mitochondrial myopathy) segmental muscle fiber necrosis is accompanied by high concentration of alpha beta/alpha TCR epitopes in the intact fiber ends, which are the target sites of myogenesis. The same sites are invaded by OKM5+ endomysial capillary sprouts that terminate at the tip of the alpha beta/alpha TCR reactive fiber ends. These hitherto unrecognized initial events of segmental muscle regeneration seem to be followed by fragmentation of the invasive capillaries into single endothelial cells, which then switch from the OKM5+ Leu19- through the OKM5+ Leu19+ to the OKM5- Leu19+ phenotype. This cell type exhibits the typical features of Leu19+ myogenic stem cells described earlier. The findings may give rise to a concept of muscle repair, in which the alpha beta/alpha TCR-related antigen, concentrated in fiber stumps, might provide positional information for invading endothelial cells. These cells appear to be a source of myogenic stem cells for regeneration.
Schubert
W
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Department of Molecular Neuropathology, University of Heidelberg, Germany.
D000328:Adult; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D018955:CD36 Antigens; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000276:immunology; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology; D017240:Mitochondrial Myopathies / Q000276:immunology; D009132:Muscles / Q000276:immunology / Q000502:physiology*; D009136:Muscular Dystrophies / Q000276:immunology; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012038:Regeneration / Q000276:immunology*; D013234:Stem Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015415:Biomarkers; D018955:CD36 Antigens; D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta