In order for a foreign protein antigen to be recognized by a T cell, it must be degraded into small antigenic peptides that form complexes with class I or class II MHC molecules. This conversion of proteins into MHC-associated peptide fragments is called antigen processing and presentation. Whether a particular antigen will be processed and presented together with class I MHC or class II MHC molecules appears to be determined by the route that the antigen takes to enter a cell (Figure 1-9).
Exogenous antigen is produced outside of the host cell and enters the cell by endocytosis or phagocytosis. Antigen-presenting cells (macrophages, dendritic cells, and B cells) degrade ingested exogenous antigen into peptide fragments within the endocytic processing pathway. Experiments suggest that class II MHC molecules are expressed within the en-docytic processing pathway and that peptides produced by degradation of antigen in this pathway bind to the cleft within the class II MHC molecules. The MHC molecules bearing the peptide are then exported to the cell surface.
Since expression of class II MHC molecules is limited to antigen-presenting cells, presentation of exogenous peptide-class II MHC complexes is limited to these cells. T cells displaying CD4 recognize antigen combined with class II MHC molecules and thus are said to be class II MHC restricted. These cells generally function as T helper cells.
Endogenous antigen is produced within the host cell itself. Two common examples are viral proteins synthesized within virus-infected host cells and unique proteins synthesized by cancerous cells. Endogenous antigens are degraded into peptide fragments that bind to class I MHC molecules within the endoplasmic reticulum. The peptide-class I MHC complex is then transported to the cell membrane. Since all nucleated cells express class I MHC molecules, all cells producing endogenous antigen use this route to process the antigen. T cells displaying CD8 recognize antigen associated with class I MHC molecules and thus are said to be class I MHC restricted. These cytotoxic T cells attack and kill cells displaying the antigen-MHC class I complexes for which their receptors are specific.
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