Toll-like receptor recognition regulates immunodominance in an antimicrobial CD4+ T cell response.
Although Toll-like Receptors (TLRs) play a major function in innate recognition of pathogens, their role in antigen processing and presentation in vivo is poorly understood. Here we establish that Toxoplasma gondii profilin, a TLR11 ligand present in the parasite, is an immunodominant antigen in the CD4(+) T cell response to the pathogen. The immunogenicity of profilin was entirely dependent on both TLR11 recognition and signaling through the adaptor myeloid differentiation factor 88 (MyD88). Selective responsiveness to this parasite protein was regulated at the level of antigen presentation by dendritic cells (DC) and required both TLR signaling and major histocompatibility complex (MHC) class II recognition acting in cis. These findings support a major influence of TLR recognition in antigen presentation by DC in vivo and establish a mechanism by which TLR ligand association regulates the immunogenicity of microbial antigens.
Yarovinsky
Felix
F
Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kanzler
Holger
H
Hieny
Sara
S
Coffman
Robert L
RL
Sher
Alan
A
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008817:Mice, Mutant Strains; D053594:Myeloid Differentiation Factor 88; D051304:Profilins / Q000276:immunology*; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000953:Antigens, Protozoan; D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D000949:Histocompatibility Antigens Class II; D008024:Ligands; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051304:Profilins; C482903:Tlr11 protein, mouse; D051193:Toll-Like Receptors