In vivo administration of major histocompatibility complex class I-specific peptides from influenza virus induces specific cytotoxic T cell hyporesponsiveness.

We have been investigating the immunogenicity of two class I major histocompatibility complex-specific peptides with a sequence derived from influenza virus nucleoprotein specific for Kd and one for Db. Peptide-modified splenocytes are unable to immunize for a primary cytotoxic T (Tc) cell response in vivo, or secondary response in vitro. Peptide-modified stimulator cells can boost virus-primed splenocytes for a strong secondary response in vitro. Animals primed with syngeneic peptide-modified splenocytes upon challenge with virus in vivo do not generate strong secondary Tc cell responses on day 3 after challenge in contrast to virus primed animals. Day 6 responses of virus-challenged, peptide-primed animals are reduced as compared to unprimed mice. This hyporesponsiveness is independent of CD8+ T cells in the priming population and can be elicited with tumor cell lines. The data are discussed in the framework of the two-signal model of immune induction.