期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 208, 期 9, 页码 1741-1747出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20110665
关键词
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资金
- Howard Hughes Medical Institute KwaZulu-Natal Research Institute for Tuberculosis and HIV
- Harvard University Initiative for Global Health
- Burroughs Wellcome Fund program in Translational Research
- National Institutes of Health [T-32 AI 007306-22, T-32 AR 007530-23, R01 AI49313, R01AR 048632, K08 AI089858, R01 CA58896]
Microbial 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.
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