Differential regulation of Th1 and Th2 cells by p91–110 and p21–40 peptides of the 16-kD α-crystallin antigen ofMycobacterium 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.