Autoreactive T cells in rheumatic disease. II. Function and specificity of an autoreactive T helper cell clone...

T cell lines were established by limiting dilution of peripheral blood (PBL) and synovial fluid lymphocytes (SFL) of a patient with HLA-B27+ reactive arthritis. Among these cell lines, the CD4 phenotype was dominant. Functionally, the majority of these cell lines exhibited helper activity for the immunoglobulin production by autologous B cells and proliferated in response to autologous mononuclear cells. In most cases, this autoreactive response was associated with alloreactivity. Only one cell line, the autoreactive CD4+ T cell clone, UA-S2, which was derived from the synovial fluid, proliferated in a highly specific manner in response to a determinant associated with MHC class II products present on autologous mononuclear cells. The restriction element was shown to be associated with DR molecules by inhibition experiments with monoclonal antibodies. Within the patient's family, the capacity of mononuclear cells to stimulate a proliferative response of UA-S2 segregated together with the HLA haplotype A2 or 32, B27, Cw1, DRw11 which was contributed by the patient's mother. UA-S2 proved to be a functional helper T cell clone. In the absence of additional antigen or mitogen, it induced IgG and IgM synthesis of autologous and family members' B cells. This helper activity of UA-S2 showed the same MHC restriction as the proliferative response. Although the patient's father also typed DRw11, this haplotype was not recognized by UA-S2. It is suggested that this autoreactive T cell clone detects a microheterogeneity of the serologically defined DRw11 haplotype. Indeed, typing of the patient's family members with cellular reagents established a difference between the two DRw11 haplotypes.