Ex vivo peptide-MHC II tetramer analysis reveals distinct end-differentiation patterns of human pertussis-specific CD4(+) T cells following clinical infection.
Pertussis is occurring in highly vaccinated populations, suggesting insufficient protective memory CD4(+) T cells to Bordetella (B.) pertussis. P.69 Pertactin (P.69 Prn) is an important virulence factor of B. pertussis, and P.69 Prn7-24 is an immunodominant CD4(+) T cell epitope in mice and broadly recognized in humans. P.69 Prn7-24 peptide-MHC II tetramers (DRB4*0101/IVKT) were designed to ex vivo interrogate the presence and differentiation state of P.69 Prn7-24 specific CD4(+) T cells in six symptomatic pertussis cases. Cases with relatively more CD45RA(-)CCR7(+) central memory CD4(+)DRB4*0101/IVKT(+) T cells secreted Th1 cytokines, while cases with more CD45RA(-)CCR7(-) effector memory CD4(+)DRB4*0101/IVKT(+) T cells secreted both Th1 and Th2 cytokines upon peptide stimulation. CD45RA(+)CCR7(-) terminal differentiation pattern was associated with low or non-functionality based on cytokine secretion. This study provides proof of principle for further peptide-MHC II tetramer guided approaches in the elucidation of limited immunological memory to B. pertussis and the resurgence of pertussis.
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Electronic address: wanda.han@rivm.nl.
Wanda G H
WG
Han
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Kina
K
Helm
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Martien M C
MM
Poelen
Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Henny G
HG
Otten
Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Cécile A C M
CA
van Els
D000293:Adolescent; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes; D002648:Child; D002675:Child, Preschool; D018984:Epitopes, T-Lymphocyte; D005260:Female; D059811:HLA-DRB1 Chains / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D037342:Pertussis Toxin / Q000276:immunology; D010566:Virulence Factors, Bordetella / Q000276:immunology; D014917:Whooping Cough / Q000276:immunology*; D055815:Young Adult
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; C487016:HLA-DRB4*01:01 antigen; D010566:Virulence Factors, Bordetella; C068929:pertactin; D037342:Pertussis Toxin
CD4; CD4 memory differentiation; Peptide-MHC class II tetramers; Pertussis; T cell clone; T cell epitope