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Characterization of T cells specific for CFP-10 and ESAT-6 in M. tuberculosis-infected Mauritian Cynomolgus Macaques.

Research paper by Amy A Ellis, Alexis A Balgeman, Mark M Rodgers, Cassaundra C Updike, Jaime J Tomko, Pauline P Maiello, Charles A CA Scanga, Shelby L SL O'Connor

Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: Infection and immunity



Abstract

Nonhuman primates can be used to study host immune responses to Mycobacterium tuberculosis (Mtb). Mauritian cynomolgus macaques (MCMs) are a unique group of animals that have limited MHC genetic diversity, such that MHC-identical animals can be infected with Mtb. Two MCMs homozygous for the relatively common M1 MHC haplotype were bronchoscopically infected with 41 colony-forming units (CFU) Mtb, Erdman strain. Four other MCMs, which had at least one copy of the M1 MHC haplotype, were infected with a lower dose of 3 CFU Mtb. All animals mounted similar T cell responses to CFP-10 and ESAT-6. Two epitopes in CFP-10 were characterized and the MHC class II alleles restricting them were determined. A third epitope in CFP-10 was identified, but exhibited promiscuous restriction. The CFP-10 and ESAT-6 antigenic regions targeted by T cells in MCMs were comparable to those seen in cases of human Mtb infection. Our data lays the foundation for generating tetrameric molecules to study epitope-specific CD4 T cells in Mtb infected MCMs, which may guide future testing of Tuberculosis vaccines in nonhuman primates.