IN-VIVO ADMINISTRATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-SPECIFIC PEPTIDES FROM INFLUENZA-VIRUS INDUCES SPECIFIC CYTOTOXIC T-CELLHYPORESPONSIVENESS

We have been investigating the immunogenicity of two class I major his tocompatibility complex-specific peptides with a sequence derived from influenza virus nucleoprotein specific for K(d) and one for D(b). Pep tide-modified splenocytes are unable to immunize for a primary cytotox ic T (Tc) cell response in vivo, or secondary response in vitro. Pepti de-modified stimulator cells can boost virus-primed splenocytes for a strong secondary response in vitro. Animals primed with syngeneic pept ide-modified splenocytes upon challenge with virus in vivo do not gene rate strong secondary Tc cell responses on day 3 after challenge in co ntrast to virus primed animals. Day 6 responses of virus-challenged, p eptide-primed animals are reduced as compared to unprimed mice. This h yporesponsiveness is independent of CD8+ T cells in the priming popula tion and can be elicited with tumor cell lines. The data are discussed in the framework of the two-signal model of immune induction.