Identification of antigen-specific B cell receptor sequences using public repertoire analysis.
High-throughput sequencing allows detailed study of the BCR repertoire postimmunization, but it remains unclear to what extent the de novo identification of Ag-specific sequences from the total BCR repertoire is possible. A conjugate vaccine containing Haemophilus influenzae type b (Hib) and group C meningococcal polysaccharides, as well as tetanus toxoid (TT), was used to investigate the BCR repertoire of adult humans following immunization and to test the hypothesis that public or convergent repertoire analysis could identify Ag-specific sequences. A number of Ag-specific BCR sequences have been reported for Hib and TT, which made a vaccine containing these two Ags an ideal immunological stimulus. Analysis of identical CDR3 amino acid sequences that were shared by individuals in the postvaccine repertoire identified a number of known Hib-specific sequences but only one previously described TT sequence. The extension of this analysis to nonidentical, but highly similar, CDR3 amino acid sequences revealed a number of other TT-related sequences. The anti-Hib avidity index postvaccination strongly correlated with the relative frequency of Hib-specific sequences, indicating that the postvaccination public BCR repertoire may be related to more conventional measures of immunogenicity correlating with disease protection. Analysis of public BCR repertoire provided evidence of convergent BCR evolution in individuals exposed to the same Ags. If this finding is confirmed, the public repertoire could be used for rapid and direct identification of protective Ag-specific BCR sequences from peripheral blood.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford OX3 7LE, United Kingdom.
Johannes
J
Trück
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford OX3 7LE, United Kingdom.
Maheshi N
MN
Ramasamy
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford OX3 7LE, United Kingdom.
Jacob D
JD
Galson
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
Richard
R
Rance
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom.
Julian
J
Parkhill
The Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom.
Gerton
G
Lunter
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford OX3 7LE, United Kingdom.
Andrew J
AJ
Pollard
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford OX3 7LE, United Kingdom.
Dominic F
DF
Kelly
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology; D018073:Haemophilus Vaccines / Q000276:immunology; D019741:Haemophilus influenzae type b / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D022401:Meningococcal Vaccines / Q000276:immunology; D008875:Middle Aged; D011135:Polysaccharides, Bacterial / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D020539:Sequence Analysis, Protein; D013745:Tetanus Toxoid / Q000276:immunology; D017778:Vaccines, Combined / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology*; D055815:Young Adult
D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D011947:Receptors, Antigen, B-Cell; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; C037676:meningococcal group C polysaccharide; C052181:meningococcal group C polysaccharide-tetanus toxoid conjugate