RECEPTOR-MEDIATED ANTIGEN DELIVERY INTO MACROPHAGES - COMPLEXING ANTIGEN TO ALPHA(2)-MACROGLOBULIN ENHANCES PRESENTATION TO T-CELLS

Macrophages secrete alpha2-macroglobulin (alpha2M), a protein that may facilitate early Ag handling. Alpha2M is able to entrap and form covalent linkages with diverse proteins during a transient proteinase-activated state. The resulting complexes are rapidly endocytosed after binding to high affinity receptors. Such a system could be capable of efficiently delivering a multitude of proteins to macrophages. We have used T hybridoma clones that respond only to hen egg lysozyme, in a MHC-restricted manner, to probe the effect of complex formation on Ag uptake and processing by murine macrophages. Radiolabeled lysozyme was internalized more rapidly and to a greater extent when bound to alpha2M than when unbound. Macrophages pulsed with lysozyme-alpha2M-elastase complexes required 200 to 250 times less Ag than those pulsed with free lysozyme to achieve effective presentation to T cells. Adding equimolar amounts of alpha2M-elastase complexes, or of alpha2M-methylamine, to free lysozyme had no effect on basal lysozyme presentation. Receptor-recognized forms of alpha2M, but not lysozyme or BSA, competed effectively for both uptake and presentation of lysozyme-alpha2M-elastase complexes. These results indicate that proteinase-activated alpha2M can enhance Ag processing by carrying Ag into macrophages through a receptor-mediated process.