ANTIGEN-PROCESSING AND PRESENTATION BY A MURINE MYOBLAST CELL-LINE

The ability of non-professional antigen-presenting cells (APC) to proc ess and present antigen to the immune system has been the subject of d ebate in autoimmunity and tumour immunology, The role of muscle cells in the processing and presentation of antigen to T cells via class I a nd class II MHC pathways is of increasing interest. Muscle cells are t he targets of autoimmune attack in the inflammatory muscle diseases, a nd direct intramuscular injection of antigen-expressing DNA constructs is under scrutiny as a means of vaccination. Furthermore, the immunol ogical properties of muscle cells are of relevance in attempts to tran sfer myoblasts as replacement cells in dystrophic diseases or as depot cells for the secretion of certain molecules in deficiency states, Us ing class I and class II MHC transfectant clones of the C2C 12 myoblas t cell line, myoblasts have been shown to be capable of presenting ant igen to, and stimulating secretion of IL-2 by, T cell hybridomas via b oth of these pathways. The epitopes which are dominantly presented by professional APC after processing of native antigens were also present ed by the myoblast cell line after processing of either ovalbumin (cla ss I) or hen egg lysozyme (class II). Further, antigen processing and presentation via the class II pathway were enhanced by pretreatment of the myoblasts with interferon-gamma (IFN-gamma). Up-regulation of inv ariant chain expression by this treatment may have contributed to this enhanced presentation, but an effect of IFN-gamma on the expression o f other molecules such as H-2 DM may have also played 3. role. The dem onstration of the antigen-presenting properties of these myoblasts is of relevance to all three areas mentioned above. In each situation myo blasts comprise a significant population within muscle. In the case of inflammatory muscle diseases the process of muscle degeneration and r egeneration is on-going, while in the vaccination procedure some muscl e damage occurs, and vaccination is more effective when muscle damage has preceded inoculation.