Differential regulation of Th1 and Th2 cells by p91-110 and p21-40 peptides of the 16-kD alpha-crystallin antigen of Mycobacterium tuberculosis.
Permissively recognized peptides which can activate lymphocytes from subjects with a variety of class II HLA types are interesting diagnostic and vaccine candidates. In this study we generated T helper clones reactive to the permissively recognized p21-40 and p91-110 peptides of the 16-kD heat shock protein of Mycobacterium tuberculosis. All the clones specific for p91-110 secreted interferon-gamma (IFN-gamma) and were of the Th1 phenotype. By contrast, the p21-40 peptide favoured the generation of IL-4-producing clones. Antibody blockade established that the peptide-specific Th clones could either be DR-, DP- or DQ-restricted. Thus, two permissively recognized sequences p21-40 and p91-110 from the same mycobacterial antigen can drive the differentiation of functionally distinct T helper subsets. Attempts to immunize against tuberculosis should bear in mind epitope specificity if a favourable Th subtype response is to be generated.
Agrewala
J N
JN
Tuberculosis & Related Infections Unit, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Wilkinson
R J
RJ
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D006682:HLA-DP Antigens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000942:Antigens, Bacterial; D016207:Cytokines; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D010446:Peptide Fragments; C072681:Mycobacterium tuberculosis antigens