MHC-restricted recognition of immunogenic T cell epitopes of pertussis toxin reveals determinants in man distinct from the ADP-ribosylase active site.
The S1 subunit of Pertussis toxin (PT) is responsible for the reactogenicity and in part the immunogenicity of Bordetella pertussis vaccine. The critical residues associated with the immunomodulatory effects of PT were located around Glu140 in the S1 subunit. In man, T cell responses to PT are directed at S1 peptides distinct from Glu140. Two such epitopes, p64-75 and p151-161, are immunogenic in a panel of individuals covering a wide range of HLA genotypes. The response to PT peptides is HLA class II restricted. The response to p64-75 is blocked by an anti-HLA-DQ mAb, while that to p151-161 is blocked by an anti-HLA-DR mAb. These findings may allow for the development of a B. pertussis vaccine free from reactogenicity.
Oksenberg
J R
JR
Department of Neurology, Stanford University, California 94305.
Judd
A K
AK
Ko
C
C
Lim
M
M
Fernandez
R
R
Schoolnik
G K
GK
Steinman
L
L
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology; D001665:Binding Sites; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology; D010430:Pentosyltransferases / Q000276:immunology; D037342:Pertussis Toxin; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides; D014614:Vaccines, Synthetic; D010566:Virulence Factors, Bordetella; D010430:Pentosyltransferases; D037342:Pertussis Toxin