Facts on the fragmentation of antigens in presenting cells, on the association of antigen fragments with MHC molecules in cell-free systems, and speculation on the cell biology of antigen processing

Abstract

The processing of a protein antigen is a multi-step event taking place in antigen-presenting cells. Processing is a prerequisite for the recognition of most antigens by T lymphocytes. The antigen is ingested by endocytosis, transported to an acid cellular compartment and subjected to proteolytic fragmentation. Some of the antigen fragments bind to MHC class II molecules and are transported to the surface of the antigen-presenting cell where the actual presentation to T lymphocytes occurs. The nature of the processed antigen, how and where it is derived and subsequently becomes associated with MHC molecules are the questions discussed in this review. To us, the entire concept of processing has appeal not only because it explains some hitherto well-established, but poorly understood, phenomena such as the fact that T lymphocytes focus their attention entirely upon antigens on other cells. It has appeal also because processing allows for a thorough scrutiny of all the proteins of a cell including both the proteins which have been taken up from the environment (mostly MHC class II-restricted) and the cell's own proteins (mostly MHC class I-restricted). Through the mechanism of processing fragments of all these proteins including "internal" fragments which are not present on the globular protein's surface are brought out on the cell surface in association with MHC molecules and displayed to the T-lymphocyte system. This allows for the identification and, if necessary, the destruction of cells which in their interior harbor abnormal proteins, be they derived from virus-encoded genes or other abnormal genes.