A NONIMMUNODOMINANT NUCLEOPROTEIN-DERIVED PEPTIDE IS PRESENTED BY INFLUENZA-A VIRUS-INFECTED H-2(B) CELLS

Influenza A virus-infected H-2(b) mice mount a CTL response directed against the nucleoprotein (NP) 366-374 but not against the NP 55-63 peptide, although both peptides fulfill the prerequisites for having high binding affinity toward the D-b molecule. Two hypotheses have been proposed to explain the inability of B6 mice to respond to the NP 55-63 peptide: 1) B6 mice are tolerant to the NP 55-63 peptide and 2) NP 55-63 peptide is not naturally processed by H-2(b) cells. Our results show that 1) B6 mice possess a NP 55-63-specific CTL repertoire because their immunization with the NP 55-63 peptide itself recruits specific CTL; 2) NP 55-63 peptide is naturally processed by the virus-infected H-2(b) cells but its efficient presentation by the D-b molecule requires higher amounts of NP than presentation of the NP 366-374 peptide; 3) NP 55-63 peptide is naturally presented in virus infected B6 mice, however, the quantity of D-b/NP 55-63 complexes at the cell surface is sufficient to tolerize but not to recruit and stimulate specific CTL; and 4) NP 55-63 peptide binds to the D-b molecule with a lower affinity than NP 366-374 does and this difference could explain the inefficient presentation of the NP 55-63 peptide by B6 cells. The involvement of the self-protein-derived nonimmunodominant peptides in self-tolerance and the possibility of using nonimmunodominant peptides of viral proteins for peptide vaccination are discussed.