A cytolytic human T lymphocyte clone differentially recognizing HLA-B27 subtypes

A cytolytic human T cell (CTL) clone, designated F/M-F159, has been produced, the lytic specificity of which distinguishes subtypes of HLA-B27. This was demonstrated in cell-mediated lympholysis (CML) assays of: 1) a panel of target cells from unrelated donors, 75 B27 + and 36 B27−; 2) six families, including 20 B27+ and 14 B27− individuals; and 3) B27+ and B27− variants of a B27+ lymphoblastoid cell line (LCL). Specificity of F/M-F159 for HLA-B27 was confirmed by blocking studies with monoclonal antibodies. Lysis of B27+ targets reactive with the anti-B27 monoclonal antibody B27M2 was 30–104%, while lysis of B27+,B27M2− targets was 4–22%. Lysis of B27- targets expressing HLA-Bw47, known to be cross-reactive with the B27M2 antibody, was 10 to 19%, while lysis of all other B27 - targets was ⩽10%. Clone F/M-F159 lysed B27+ targets, and failed to lyse B27-targets, irrespective of the clinical status of the cell donors. It is concluded that F/M-F159 recognizes an epitope present on the majority of serologically identified HLA-B27 molecules and that this epitope is close related to, but not identical with, the epitope recognized by the antibody B27M2. These findings are interpreted as supporting a direct role for HLA-B27 in disease pathogenesis.