Nov 4, 2015

The TB-specific CD4(+) T cell immune repertoire in both cynomolgus and rhesus macaques largely overlap with humans

Tuberculosis
Bianca R MothéAlessandro Sette

Abstract

Non-human primate (NHP) models of tuberculosis (TB) immunity and pathogenesis, especially rhesus and cynomolgus macaques, are particularly attractive because of the high similarity of the human and macaque immune systems. However, little is known about the MHC class II epitopes recognized in macaques, thus hindering the establishment of immune correlates of immunopathology and protective vaccination. We characterized immune responses in rhesus macaques vaccinated against and/or infected with Mycobacterium tuberculosis (Mtb), to a panel of antigens currently in human vaccine trials. We defined 54 new immunodominant CD4(+) T cell epitopes, and noted that antigens immunodominant in humans are also immunodominant in rhesus macaques, including Rv3875 (ESAT-6) and Rv3874 (CFP10). Pedigree and inferred restriction analysis demonstrated that this phenomenon was not due to common ancestry or inbreeding, but rather presentation by common alleles, as well as, promiscuous binding. Experiments using a second cohort of rhesus macaques demonstrated that a pool of epitopes defined in the previous experiments can be used to detect T cell responses in over 75% of individual monkeys. Additionally, 100% of cynomolgus macaques, irrespective of thei...Continue Reading

Mentioned in this Paper

ESAT gene
Immune Response
Pathogenic Aspects
Immune System
T-Lymphocyte
Pathogenesis
Tuberculosis
N-3-(4-hydroxyphenyl)propionyl-prolyl-hydroxyprolyl-glycyl-alanyl-glycine
Spleen
Pathogenic Organism

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