ANALYSIS OF CYTOTOXIC T-CELL RESPONSES TO DOMINANT AND SUBDOMINANT EPITOPES DURING ACUTE AND CHRONIC LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTION

The cytotoxic T cell response against lymphocytic choriomeningitis vir us (LCMV) in BALB/c (H-2(d)) mice is predominantly directed against a single immunodominant L(d)-restricted epitope in the viral nucleoprote in (NP118-126). Here we report that the immunodominance of this peptid e can be in part attributed to its very high affinity for L(d) class I molecules, By employing motif searches and sensitive MHC class I bind ing assays, we also identified 5 K-d-binding peptides in the viral nuc leoprotein and glycoprotein among 16 K-d motif-fitting peptides. The n ucleoprotein and glycoprotein sequences also contained 18 D-d motif-fi tting peptides, three of which bound D-d with weak affinity. Two of th e K-d-binding peptides, residues 99-108 and residues 283-291 from the viral glycoprotein, are subdominant epitopes, Although these peptides did not sensitize target cells for direct ex vivo killing by primary a ntiviral CTL, secondary responses against these peptides were readily detected in BALB/c mice after acute LCMV infection, BALB/c mice that h ad cleared a long-term LCMV infection showed more sustained CTL respon ses against these subdominant epitopes, suggesting that subdominant re sponses might play a role in clearance of chronic infections, One of t he subdominant epitopes, GP(283-291), conferred partial protection aga inst persistent viral infection after peptide vaccination.