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.