The subdiscipline of tumor immunology involves the study of antigens on tumor cells and the immune response to these antigens. Two types of tumor antigens have been identified on tumor cells: tumor-specific transplantation antigens (TSTAs) and tumor-associated transplantation antigens
(TATAs). Tumor-specific antigens are unique to tumor cells and do not occur on normal cells in the body. They may result from mutations in tumor cells that generate altered cellular proteins; cytosolic processing of these proteins would give rise to novel peptides that are presented with class I MHC molecules, inducing a cell-mediated response by tumor-specific CTLs (Figure 22-6). Tumor-associated antigens, which are not unique to tumor cells, may be proteins that are expressed on normal cells during fetal development when the immune system is immature and unable to respond but that normally are not expressed in the adult. Reactivation of the embryonic genes that encode these proteins in tumor cells results in their expression on the fully differentiated tumor cells. Tumor-associated antigens may also be proteins that are normally expressed at extremely low levels on normal cells but are expressed at much higher levels on tumor cells. It is now clear that the tumor antigens recognized by human T cells fall into one of four major categories:
■ Antigens encoded by genes exclusively expressed by tumors
■ Antigens encoded by variant forms of normal genes that have been altered by mutation
■ Antigens normally expressed only at certain stages of differentiation or only by certain differentiation lineages
■ Antigens that are overexpressed in particular tumors
Many tumor antigens are cellular proteins that give rise to peptides presented with MHC molecules; typically, these antigens have been identified by their ability to induce the proliferation of antigen-specific CTLs or helper T cells.
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