THE MOLECULAR-BASIS OF MHC-MEDIATED ANTIGEN PRESENTATION AND CELLULAR-RESPONSE IN NORMAL AND CANCER-CELLS

Cytotoxic T lymphocytes recognize host cells that express new antigens as a result either of viral infection or transformation. Protein anti gens are first degraded into fragments in cell cytoplasms, then transp orted to the endoplasmatic reticulum and eventually expressed on the c ell surface, accomodated in a deep groove of class I molecules of the major histocompatibility complex. Even in absence of exogenous protein s, MHC molecules on the cell surface carry a large number of peptides derived from endogenous proteins. The isolation of such peptides, and the determination of their chemical structures, has permitted the iden tification of the characteristics ''anchor motifs'' for different MHC alloantigens. In these last years, there has been an increasing intere st in the identification of peptides expressed preferentially or exclu sively by cancer cells, since this information might help in finding a specific immunotherapy for malignant diseases. Several approaches hav e been used for this study, including the elution of peptides from MHC of tumor cells, followed by their purification, and by a test on thei r ability to render target cells susceptible to tumor-specific cytotox ic T lymphocytes; the synthesis of peptides known to be tumor-specific or tumor-dominant, followed by a test for their ability to activate a tumor-specific response has also been utilized. The complex mechanism s connected with cytotoxic T cells activation has been as well partly elucidated. All these data, although fragmentary and incomplete, allow a first insight into the complexity of the problems connected with ce llular response to cancer, and partly explain the failure of cell defe nce against cancer progression.