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Jacobs J Allergy Immunol. 2014 Sep 5;1(1):002.

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

Author information

1
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
2
Department of Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN 55905.

Abstract

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.

KEYWORDS:

CFP-10; HLA; Tuberculosis; humanized mice ESAT-6

PMID:
25664343
PMCID:
PMC4316384

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