The presentation of exogenous foreign antigens to CD4-positive T-cells involves a complex series of events that includes the endocytosis of intact antigen, its proteolytic processing into peptides that then bind to newly synthesized MHC class II molecules, and the subsequent expression of the immunogenic class II-peptide complexes on the plasma membrane. While the general features of this pathway have been known for years, there is little precise information or agreement concerning the cell biological basis underlying each of these steps. Among the more critical issues remaining unresolved are the actual intracellular site(s) in which antigen processing and peptide-MHC complex formation occurs, whether accessory proteins exist that help select and/or transfer immunogenic peptides onto class II molecules, how proteins involved in antigen processing and presentation are targeted to their appropriate destinations, and whether the endocytic pathway in professional antigen- presenting cells is specialized to help mediate these events. Recently, strategies combining the techniques of cell biology and genetics with those of immunology have yielded significant new insights into class II- restricted antigen presentation. Specifically, it seems likely that at least some antigen-presenting cells contain a novel population of MHC class II vesicles (CIIV or MIIC) that serves as an important site for the formation of peptide
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