MOLECULAR ANALYSIS OF THE IMMUNE-RESPONSE TO HUMAN CYTOMEGALOVIRUS GLYCOPROTEIN-B .1. MAPPING OF HLA-RESTRICTED HELPER T-CELL EPITOPES ON GP93

Human cytomegalovirus (HCMV) is one of the most common causes of conge nital infection leading to birth defects, and a leading cause of serio us illness in patients with impaired cell-mediated immunity. Helper T cell (T(h)) responses to HCMV proteins are likely to be important in l imiting viral replication and preventing disease. Previous studies fro m this laboratory have demonstrated that the amino-terminal 513 amino acids of HCMV glycoprotein B (gB) can stimulate both B and T cell resp onses in humans. In the present study, the proliferative responses of HCMV-specific T(h) clones to recombinant proteins and synthetic peptid es were examined to identify four T(h) epitopes on gp93, which represe nts the amino-terminal 460 amino acids of the gB polypeptide. Using cl ones of known HLA restriction specificity from several donors, it was shown that each HLA class II allele preferentially associates with a d ifferent epitope on gB. Five clones from two different donors recogniz ed an epitope in the region of amino acids 250 to 264 restricted by DR 4Dw14. two clones from different donors recognized an epitope in the r egion of amino acids 420 to 434 restricted by DR7Dw17, two clones from different donors recognized an epitope in the region of amino acids 1 78 to 194 restricted by DQw1 and a single clone recognized an epitope in the region of amino acids 190 to 204 restricted by DPw4. Although a ll peripheral blood mononuclear cells (PBMCs) expressing a particular HLA class II allele were able to present the appropriate HLA-restricte d gB peptide to gB-specific T(h) clones, not all individuals expressin g a given HLA allele exhibited PBMC responses to the corresponding gB peptide. The HLA-related differences in T(h) recognition of specific e pitopes on gB described in this report may have important implications in virus-host interactions and vaccine strategies.