With a goal of enhancing endogenous antigen trafficking to the cellular MHC II compartment of antigen-presenting cells, we employ the use of genetic vaccines encoding the antigens as chimeras containing the lysosomal targeting sequences of the lysosome-associated membrane protein (LAMP). Our rationale is that the delivery of antigen to the cellular site of MHC II processing and binding of antigen epitopes could result in an enhanced immune response through greater antigen-specific activation of CD4 ϩ T-cells. LAMP molecules have steady-state localization in the outer membrane of lysosomes (15-17) with a trafficking pathway from the Golgi complex (18, 19) mediated by adaptor protein binding (20) to the carboxyl-terminal YXXØ (where the Ø symbol represents any hydropholic amino acid) recognition sequence of an 11-amino acid cytoplasmic tail (21-23). This LAMP trafficking pathway was found to coincide with that of MHC II in specialized multilaminar vesicular compartments of immature APCs, termed MIIC, sites associated with the formation of antigenic peptide-MHC II complexes (24 -28).
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