Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ Th1 subset.
An understanding of the immunological footprint of Mycobacterium tuberculosis (MTB) CD4 T cell recognition is still incomplete. Here we report that human Th1 cells specific for MTB are largely contained in a CXCR3(+)CCR6(+) memory subset and highly focused on three broadly immunodominant antigenic islands, all related to bacterial secretion systems. Our results refute the notion that secreted antigens act as a decoy, since both secreted proteins and proteins comprising the secretion system itself are targeted by a fully functional T cell response. In addition, several novel T cell antigens were identified which can be of potential diagnostic use, or as vaccine antigens. These results underline the power of a truly unbiased, genome-wide, analysis of CD4 MTB recognition based on the combined use of epitope predictions, high throughput ELISPOT, and T cell libraries using PBMCs from individuals latently infected with MTB.
La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
Cecilia S
CS
Lindestam Arlehamn
Anna
A
Gerasimova
Federico
F
Mele
Ryan
R
Henderson
Justine
J
Swann
Jason A
JA
Greenbaum
Yohan
Y
Kim
John
J
Sidney
Eddie A
EA
James
Randy
R
Taplitz
Denise M
DM
McKinney
William W
WW
Kwok
Howard
H
Grey
Federica
F
Sallusto
Bjoern
B
Peters
Alessandro
A
Sette
D000328:Adult; D000368:Aged; D016680:Genome, Bacterial; D055106:Genome-Wide Association Study; D054884:Host-Pathogen Interactions; D006801:Humans; D007156:Immunologic Memory; D055985:Latent Tuberculosis / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
C106311:CCR6 protein, human; C515187:CXCR3 protein, human; D054399:Receptors, CCR6; D054367:Receptors, CXCR3