A lectin-binding, protease-resistant mycobacterial ligand specifically activates V gamma 9+ human gamma delta T cells.
Bacterial (exogeneous) superantigens have been defined as bifunctional proteinaceous molecules. They bind to class II MHC molecules of presenting cells and engage with particular TCR-V beta gene elements, thereby activating alpha beta T cells in a V beta-oriented fashion. In previous studies we have elucidated that gamma delta T cells exhibit a propensity to vigorously respond toward mycobacterial Ag. Intrigued by this finding we now analyzed whether mycobacteria express a superantigen for a subset of human gamma delta T cells definable by the selective use of TCR-V gene elements. Here we describe that a protease-resistant, low m.w. (1 to 3 kDa) component of mycobacteria selectively activates gamma delta T cells expressing TCR-V gamma 9 gene segments. Contained in mycobacterial lysates it stimulates TCR-V gamma 9-positive gamma delta T cells at a frequency of 1/6. Stimulation is critically dependent on the presence of class II MHC-positive presenting cells, the important structure being HLA-DR molecules. The fine specificity of the V gamma 9 seeking mycobacterial ligand differs from the gamma delta T cell-stimulating structures expressed by Daudi cells. In addition, the mycobacterial, V gamma 9-seeking ligand is bound selectively to lectins such as UEAI, SBA, and DBA. We conclude that mycobacteria contain a component that acts as a superantigen for human gamma delta T cells and we believe it is this property that explains the vigorous participation of gamma delta T cells in mycobacterial infections.
Pfeffer
K
K
Institute of Medical Microbiology and Hygiene, Technical University of Munich, Germany.
Schoel
B
B
Plesnila
N
N
Lipford
G B
GB
Kromer
S
S
Deusch
K
K
Wagner
H
H
D000942:Antigens, Bacterial / Q000276:immunology*; D010450:Endopeptidases / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008213:Lymphocyte Activation; D009161:Mycobacterium / Q000276:immunology*; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D037102:Lectins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D010450:Endopeptidases