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 subjec ts with a variety of class II HLA types are interesting diagnostic and vacc ine 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 co ntrast, the p21-40 peptide favoured the generation of IL-4-producing clones . Antibody blockade established that the peptide-specific Th clones could e ither be DR-, DP- or DQ-restricted. Thus, two permissively recognized seque nces p21-40 and p91-110 from the same mycobacterial antigen can drive the d ifferentiation of functionally distinct T helper subsets. Attempts to immun ize against tuberculosis should bear in mind epitope specificity if a favou rable Th subtype response is to be generated.