Immune response to immunodominant Mycobacterium tuberculosis antigen ESAT-6 derived peptide is HLA-haplotype dependent.

The antigenic proteins of Mycobacterium tuberculosis (Mtb) have been defined. We used synthetic peptides of secreted antigens, Early Secreted Antigenic Target 6 (ESAT-6) and Cultural Filtrate Protein-10 (CFP-10), of Mtb and characterized the immune response in context of HLA genes. Humanized mice lacking endogenous class II molecules but expressing various human DR and DQ HLA transgenes singly or as a haplotype were used to study the HLA-mediated immune response to peptides. Our observations showed that the overall response to the promiscuous ESAT-6 31-45 peptide may be dependent on the HLA haplotype rather than a single DR or DQ molecule. Further, our data showed that HLA transgenes generated a highly variable TH response to this promiscuous peptide. This provides an explanation for the variability of the bacillus Calmette-Guerin (BCG) vaccine. Our data highlights the use of HLA transgenic mice for determining the pathogenicity or therapeutic nature of a peptide in the context of HLA alleles.