LOSS OF MAJOR HISTOCOMPATIBILITY COMPLEX-ENCODED TRANSPORTER ASSOCIATED WITH ANTIGEN PRESENTATION (TAP) IN COLORECTAL-CANCER

Presentation of endogenous antigenic peptides to cytotoxic T lymphocyt es (CTLs) is mediated by the major histocompatibility complex (MHC) cl ass I molecules. These antigenic peptides derived from the cytoplasmic protein pool are transported by the recently described MHC-encoded tr ansporters (TAP1 and TAP2) into a pre-Golgi region where they take par t in the assembly of MHC class I molecules. Using an affinity-purified polyclonal antibody (AK1.7) for TAP1, we analyzed 81 colorectal carci nomas, 32 adenomas, and the respective nonneoplastic mucosa. Loss of t he transporter molecule (TAP1) was observed in 14% (11 of 81) of tbe c arcinomas, either complete (7 of 11) or focal (4 of 11), whereas adeno mas and normal mucosa were always positive. This study adds further in formation to the understanding of the mechanisms related to the defect ive,e presentation of the MHC class I molecules by tumor cells.