Recognition of hepatitis B virus envelope proteins by liver-infiltrating T lymphocytes in chronic HBV infection.
The Ag specificity and cytotoxic function of human T cell clones, generated from lymphocytes infiltrating the liver of a chronic hepatitis B patient, were studied. Both class I- and class II-restricted T clones specifically proliferated to hepatitis B virus envelope proteins, but not to hepatitis B core Ag. The fine specificity of T cells was studied by using rAg having different composition in relation to HBV-envelope proteins or synthetic peptides of preS regions. The antigenic determinant recognized by T cell clones mapped to the preS2 region based on the response to r(preS1+preS2+S) and to r(preS2+S) and the failure to respond to S or preS1 alone. More precise epitope mapping was based on synthetic preS2 peptides 120-150 or 120-134, which stimulated both class I- and class II-restricted T clones, whereas preS2 153-171 or preS1 1-110 peptides did not; thus, the preS2 120-134 appears to contain both the residues binding to class I molecules and the residues binding to class II molecules. Moreover, strong and specific cytotoxic responses of these clones were observed only when HLA-matched EBV-lines, used as target cells, were previously sensitized with r(preS1+preS2+S) or preS2 peptides, which were shown to stimulate the clones. Thus, a preS2 epitope can represent a target Ag for liver-infiltrating T cells, which could kill the hepatocytes expressing the Ag plus the appropriate MHC molecule.
Barnaba
V
V
I Clinica Medica, Università La Sapienza di Roma, Italy.
Franco
A
A
Alberti
A
A
Balsano
C
C
Benvenuto
R
R
Balsano
F
F
D000328:Adult; D002465:Cell Movement; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D006521:Hepatitis, Chronic / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000939:Epitopes; D006680:HLA Antigens; D006514:Hepatitis B Surface Antigens; D014759:Viral Envelope Proteins