Cheng, Tan-YunTurner, MarieSeshadri, ChetanSchiefner, AndreKalathur, Ravi C.Annand, John W.de Jong, AnnemiekeShires, JohnWilson, Ian A.Altman, John D.Kasmar, Anne G.Van Rhijn, IldikoLeon, LuisBrenner, MichaelMoody, David2013-02-112011Kasmar, Anne G., Ildiko van Rhijn, Tan-Yun Cheng, Marie Turner, Chetan Seshadri, Andre Schiefner, Ravi C. Kalathur, et al. 2011. CD1b tetramers bind \(\alpha \beta\) T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans. The Journal of Experimental Medicine 208(9): 1741-1747.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:10288479Microbial lipids activate T cells by binding directly to CD1 and T cell receptors (TCRs) or by indirect effects on antigen-presenting cells involving induction of lipid autoantigens, CD1 transcription, or cytokine release. To distinguish among direct and indirect mechanisms, we developed fluorescent human CD1b tetramers and measured T cell staining. CD1b tetramer staining of T cells requires glucose monomycolate (GMM) antigens, is specific for TCR structure, and is blocked by a recombinant clonotypic TCR comprised of TRAV17 and TRBV4-1, proving that CD1b-glycolipid complexes bind the TCR. GMM-loaded tetramers brightly stain a small subpopulation of blood-derived cells from humans infected with Mycobacterium tuberculosis, providing direct detection of a CD1b-reactive T cell repertoire. Polyclonal T cells from patients sorted with tetramers are activated by GMM antigens presented by CD1b. Whereas prior studies emphasized CD8\(^+\) and CD4\(^-\)CD8\(^-\) CD1b-restricted clones, CD1b tetramer-based studies show that nearly all cells express the CD4 co-receptor. These findings prove a cognate mechanism whereby CD1b-glycolipid complexes bind to TCRs. CD1b tetramers detect a natural CD1b-restricted T cell repertoire ex vivo with unexpected features, opening a new investigative path to study the human CD1 system.en-USJournal Article2013-02-1110.1084/jem.20110665