Analyses of recombinant proteins isolated from genomic libraries of pathogenic organisms represent the beginning of identifying immunologically-reactive epitopes. The induction of cell-mediated and humoral immune responses to any pathogen begins with the uptake and processing of antigen by antigen-presenting cells and the display of specific epitopes to the immune system of the host. Little emphasis is placed on the molecular mechanisms underlying transport of foreign proteins into antigen-presenting cells and factors that influence degradation to the peptides which represent the epitopes that associate with newly synthesized class II molecules of the major histocompatibility complex. These cellular processes are crucial to the design of any new generation vaccine. We describe our analysis of the 18 kDa protein antigen of Mycobacterium leprae and consider a possible role for antibody in antigen-processing. In both macrophage/dendritic cells and B lymphocytes, we suggest that antibody plays a directional role in antigen uptake, subcellular compartmentalization, and antigen degradation to yield peptides. These steps will all have an impact on the construction of new generation vaccines.