Antigen processing and presentation by a murine myoblast cell line

Abstract

SUMMARY The ability of non-professional antigen-presenting cells (APC) lo process and present antigen to the immune system has been the subject of debate in autoimmunity and tumour immunology. The role of muscle cells in the processing and presentation of antigen to T cells via class 1 and class II MHC pathways is of increasing interest. Muscle cells are the targets of autoimmune attack in the inflammatory muscle diseases, and direct intramuscular injection of antigen-expressing DNA constructs is under scrutiny as a means of vaccination. Furthermore, the immunological properties of muscle cells are of relevance in attempts to transfer my oblasts as replacement cells in dystrophic diseases or as depot cells for the secretion of certain molecules in deficiency states. Using class I and class II MHC transfectant clones of the C2CI2 my oblast cell line, my oblasts have been shown to be capable of presenting antigen to. and stimulating secretion of IL-2 by, T cell hybridomas via both of these pathways. The epitopes which are dominantly presented by professional APC after processing of native antigens were also presented by the myoblast cell line after processing of either ovaibumin (class I) or hen egg lysozyme (class 11). Further, antigen processing and presentation via the class II pathway were enhanced by pretreatment of the my oblasts with interferon-gamma (IFN-γ), Up-regulation of invariant chain expression by this treatment may have contributed to this enhanced presentation, but an effect of IFN-γ on the expression of other molecules such as H-2 DM may have also played a role. The demonstration of the antigen-presenting properties of these my oblasts is of relevance to all three areas mentioned above. In each situation my oblasts comprise a significant population within muscle. In the case of inflammatory muscle diseases the process of muscle degeneration and regeneration is on-going, while in the vaccination procedure some muscle damage occurs, and vaccination is more effective when muscle damage has preceded inoculation.