AbstractAntigens coded by the major histocompatibility complex (MHC) stimulate a large number of cytotoxic T lymphocyte (CTL) precursors. Matzinger and Bevan have suggested that the high alloreactivity is a result of the formation of interaction antigens between MHC and non‐MHC‐coded antigens. Previous work by Langhorne and Fischer Lindahl did not support this hypothesis. In this report we describe an improved culture system to show that the recognition of Kktarget cells by Kk‐specific clones is also unaffected by H‐2D products. Using such a culture system, which controls for the induction of nonspecific CTL by interleukin 2 (T cell growth factor), we were also able to confirm the original conclusion of Langhorne and Fischer Lindahl that polymorphic minor histocompatibility antigens do not significantly contribute to putative “interaction antigens” formed by MHC and oth