Abstract
The requirements for the conversion of CD8^+^ memory T cells into effector class I major histocompatibility complex (MHC) K^d^−restricted cytotoxic T (T~c~) cells in vitro have been studied. Purified CD8^+^splenocytes from influenza A/WSN‐primed BALB/c (H‐2^d^) mice stimulated with a synthetic nucleoprotein peptide 147–158 R156^−^ (NPP) alone generated T~c~ cells specific for influenza virus‐infected target cells. No additional requirements for accessory cells or their lymphokine products were necessary indicating that peptide antigen (Ag) in association with K^d^ was presented on CD8^+^ T cells. The evidence for presentation of NPP by CD8^+^ T cells was supported by the use of CD8^+^ memory T cells from semiallogeneic bone marrow radiation chimeras of P~1~ → F~1~ type (H2b→ [H‐2^d^ x H‐2^b^]F~1~). Memory CD8^+^ splenocytes from A/WSN‐immune chimeras did not develop into secondary effector T~c~ cells as a result of a 4‐day culture with NPP alone, however, were able to do so if NPP was presented by K^d^−bearing Ag‐presenting cells. In addition, these results exclude the possibility of direct recognition of free NPP molecules by the specificT cell receptor of CD8^+^ memory T cells. CD8^+^ memory splenocytes (H‐2^b^) from chimeras were also able to develop into functionally active T~c~ cells as a result of presentation of D^b^−restricted synthetic peptide (NP 366–374) with a sequence derived from influenza virus nucleoprotein with high affinity for D^b^ MHC class I molecules. Blockade of endogenously produced interleukin 2 (IL‐2) activity by anti‐IL‐2 or anti‐IL‐2 receptor monoclonal antibody in the culture of CD8^+^ memory T cells during a 4‐day NPP stimulation completely abolished T~c~ cell generation, indicating that the utilization of this lymphokine is absolutely required for the secondary T~c~ cell development. These findings demonstrate that CD8^+^ memory T cells per se are able to recognize the restimulating epitope as a result of its presentation by CD8^+^ T cells and develop into cytolytically active and highly specific T~c~ cells with no requirements for other cellular helper components or their lymphokine products.