# Rare variable M. tuberculosis antigens induce predominant Th17 responses in human infection

## TL;DR

This study shows that certain tuberculosis antigens trigger Th17 immune responses in humans, which could help in developing better TB vaccines.

## Contribution

The study identifies rare variable Mtb antigens that preferentially induce Th17 responses, offering new insights for TB vaccine design.

## Key findings

- RVMA antigens induce CD4 T cells expressing RoRγt and producing IL-17 in humans recently exposed to TB.
- Classical Mtb antigens predominantly induce IFN-γ-producing T cells.
- RVMA antigens may help amplify Th17 responses to prevent TB disease progression.

## Abstract

CD4 T cells are essential for immunity to M tuberculosis (Mtb), and emerging evidence indicates that IL-17–producing Th17 cells contribute to immunity to Mtb. While identifying protective T cell effector functions is important for TB vaccine design, T cell antigen specificity is also likely to be important. To identify antigens that induce protective immunity, we reasoned that, as in other pathogens, effective immune recognition drives sequence diversity in individual Mtb antigens. We previously identified Mtb genes under evolutionary diversifying selection pressure whose products we term Rare Variable Mtb Antigens (RVMA). Here, in 2 distinct human cohorts with recent exposure to TB, we found that RVMA preferentially induce CD4 T cells that express RoRγt and produce IL-17, in contrast to “classical” Mtb antigens that induce T cells that produce IFN-γ. Together with emerging evidence showing human Th17 responses are associated with prevention of progression to TB disease, our results suggest that RVMA can be valuable antigens in vaccines for those already infected with Mtb to amplify existing antigen-specific Th17 responses to prevent TB disease.

Different individual Mycobacterium tuberculosis antigens induce distinct T cell responses, with important implications for TB vaccine development.