Van Rhijn, IldikoKasmar, Anne G.de Jong, AnnemiekeGras, StephanieBhati, MugdhaDoorenspleet, Marieke E.de Vries, NiekGodfrey, Dale I.Altman, Johnde Jager, WilcoRossjohn, JamieMoody, D. Branch2014-03-112013Van Rhijn, I., A. Kasmar, A. de Jong, S. Gras, M. Bhati, M. E. Doorenspleet, N. de Vries, et al. 2013. “A conserved human T cell population targets mycobacterial antigens presented by CD1b.” Nature immunology 14 (7): 10.1038/ni.2630. doi:10.1038/ni.2630. http://dx.doi.org/10.1038/ni.2630.1529-2908http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879627T cell receptors (TCRs) pair in millions of combinations to create complex and personally unique T cell repertoires. Using tetramers to analyze CD1b-reactive TCRs, we detected T cells with highly stereotyped TCR α chains present among genetically unrelated tuberculosis patients. These germline-encoded mycolyl-reactive (GEM) T cells were defined by CD4 expression and rearrangement of TRAV1-2 to TRAJ9 with few N-region additions. TCR analysis by high throughput sequencing, binding and crystallography showed linkage of TCR α sequence motifs to high affinity antigen recognition. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments, high affinity GEM TCRs and more diverse TCRs with low affinity for CD1b-lipid complexes. These data demonstrate high inter-donor conservation of TCRs, which likely results from selection by a non-polymorphic antigen presenting molecule and an immunodominant antigen.en-USJournal Article2014-03-1110.1038/ni.2630