DENDRITIC CELLS PULSED WITH CEA PEPTIDE INDUCE CEA-SPECIFIC CTL WITH RESTRICTED TCR REPERTOIRE

The human carcinoembryonic antigen (CEA), which is expressed in severa l cancer types is a potential target for antigen-specific immunotherap y. In this study, we show that dendritic cells (DC) pulsed with an HLA class I restricted CEA cytotoxic T lymphocyte (CTL) peptide epitope c an stimulate T cells to kill CEA peptide loaded T2 target cells as wel l as CEA expressing tumor lines in the presence of interleukin-7 (IL-7 ) in an HLA-restricted manner. This has been demonstrated for carcinom a patients as well as healthy donors. The DC-CEA + IL7 stimulated cult ures contained predominantly CD3(+)CD8(+)CD56(-) cells indicative of M HC class I resticted CTL. In addition, DC-CEA + IL-7 stimulated cells showed higher levels of CD69 expression compared with cells stimulated with IL-7 alone, implying an activated phenotype. When the T-cell rec eptor (TCR) from CTL cultures stimulated with DC-CEA + IL-7 was analyz ed, an oligoclonal pattern of expression was found for certain V beta subfamilies compared with the polyclonal patterns shown by IL-7 or phy tohemagglutinin stimulated T cells from the same donors. This TCR rest riction appeared to be maintained and enhanced after additional rounds of restimulation with DC-CEA + IL-7. The association between cytotoxi city and TCR restriction suggests that TCR analysis may be useful as a n in vitro indicator to monitor alterations in the T-cell population i n response to antigen-specific immunotherapies.