Description:
<jats:title>Summary</jats:title><jats:p>For decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that <jats:styled-content style="fixed-case">CD</jats:styled-content>1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T‐cell receptors (<jats:styled-content style="fixed-case">TCR</jats:styled-content>s) recognize <jats:styled-content style="fixed-case">CD</jats:styled-content>1‐lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the <jats:styled-content style="fixed-case">CD</jats:styled-content>1 system, and new studies done with <jats:styled-content style="fixed-case">CD</jats:styled-content>1 tetramers identify T‐cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the <jats:styled-content style="fixed-case">CD</jats:styled-content>1 and major histocompatibility complex systems is that all humans express nearly identical <jats:styled-content style="fixed-case">CD</jats:styled-content>1 proteins. Correspondingly, human <jats:styled-content style="fixed-case">CD</jats:styled-content>1 responsive T cells show evidence of conserved <jats:styled-content style="fixed-case">TCR</jats:styled-content>s. In addition to natural killer T cells and mucosal‐associated invariant T (<jats:styled-content style="fixed-case">MAIT</jats:styled-content> cells), conserved <jats:styled-content style="fixed-case">TCR</jats:styled-content>s define other subsets of human T cells, including germline‐encoded mycolyl‐reactive (<jats:styled-content style="fixed-case">GEM</jats:styled-content>) T cells. The simple immunogenetics of the <jats:styled-content style="fixed-case">CD</jats:styled-content>1 system and new investigative tools to measure T‐cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease.</jats:p>