The recognition of HLA-B27 by human CD4(+) T lymphocytes

HLA-B27 transgenic animal models suggest a role for CD4(+) T lymphocytes in the pathogenesis of the spondyloarthropathies, and murine studies have rai sed the possibility that unusual forms of B27 may be involved in disease. W e demonstrate that CD4(+) T cells capable of recognizing B27 can be isolate d from humans by coculture with the MHC class II-negative cell line T2 tran sfected with B27. These CD4(+) T cells recognize a panel of B27-transfected cell lines that are defective in Ag-processing pathways, but not the nontr ansfected parental cell lines, in a CD4-dependent fashion. Inhibition of re sponses by the MHC class I-specific mAb w6/32 and the B27 binding mAb ME1 i mplicates the recognition of a form of B27 recognized by both of these Abs. We suggest that B27-reactive CD4(+) T cells may be pathogenic in spondyloa rthropathies, particularly if factors such as infection influence expressio n of abnormal forms of B27.