A novel HLA class II-independent TCR-mediated T cell activation mechanism is distinguished by the V beta specificity of the proliferating oligoclones and their capacity to generate interleukin-2.
Superantigens can induce proliferative T cell responses after complex formation with major histocompatibility complex (MHC) class II antigens. In this study, highly purified variant T cells from a histocompatibility leukocyte antigen (HLA) (human major histocompatibility complex) class II-deficient patient were stimulated with toxic shock syndrome toxin 1 (TSST-1) in the presence of either HLA class II-negative or normal antigen-presenting cells (APC). The proliferative responses were similar to those of normal T cells even when HLA class II structures were absent on both responding T cells and costimulatory APC. However, the V beta specificity of responding T cells differed depending on the presence or absence of HLA class II antigens on the APC. In the presence of HLA class II-negative costimulatory APC, TSST-1 induced primarily proliferation of V beta 2-expressing T cells, whereas in the presence of normal APC virtually all responding T cells expressed V beta elements different from V beta 2. In addition, in the presence of normal APC, T cells responding to TSST-1 produced much higher amounts of interleukin-2 than T cells proliferating in the presence of HLA class II-negative APC. These findings suggest that T cells bearing selected V beta elements can directly interact with and respond to superantigen without involvement of HLA class II structures. Thus, our findings introduce a novel and distinct T cell receptor-mediated activation mechanism by which specific subpopulations of T cells respond to superantigen in the absence of HLA class II structures on APC.
Dennig
D
D
Sloan-Kettering Institute, Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Yan
Y
Y
Ferguson
K
K
O'Reilly
R J
RJ
D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001427:Bacterial Toxins; D002461:Cell Line, Transformed; D002999:Clone Cells; D004768:Enterotoxins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal