AbstractIn a model system for accessory cell (AC)‐dependent mitogen‐induced T cell proliferation the response of several human antigen‐specific, HLA‐restricted helper T lymphocyte clones (HTLC) to mitogens was studied. It was found that the HTLC themselves did not or only weakly respond to various mitogens or to oxidation by galactose oxidase, but that the response could be strongly increased if certain tumor cell lines were added to the assay as AC. Pretreatment with lectins or oxidation of either HTLC or AC was effective in stimulating the proliferation of the T cells in this system. Reduction of the aldehydes formed during oxidation completely abolished the stimulatory activity of oxidized B lymphoblastoid cell line. This shows that crosslinking of T cell and AC is required to induce proliferation.When several established cell lines were tested for their capacity to function as AC in this system, profound differences in AC activity were detected. The inability of cells with poor AC activity to stimulate the HTLC was not due to trivial reasons, such as requirements for different mitogen concentrations, a decreased binding of mitogens or suppressive effects. Furthermore, AC activity was not dependent on the presence of Ia antigens on the AC. These findings are discussed with regard to the mechanism of mitogen‐induced T cell a