The pathogenetic role of HLA-B27.

In order to develop a possible animal model to study H L A linked diseases of man, we established HLA-B27 transgenic mice (TGM). As aberrant and overexpression of M H C molecules can be toxic for cells, we aimed at obtaining a physiological expression of the human antigen and used a genomic 25kb Sal I fragment for embryo injection, coding for the H L A B * 2705 heavy chain. Five independent founder mice were obtained containing varying copies of the fragment (1 to 10). R N A analysis from different tissues showed an expression pattern similar to endogenous H-2 class I genes. HLA-B27 antigen could be detected on lymphocytes derived from all five founder mice, even in the absence of human ß 2-microglobulin (huß2m). It was found that the presence of huß2m strongly enhances HLA-B27 cell surface expression in mice with few copies of the transgene, but was not necessary for efficient and high cell surface presentation in the 10 copy line. In all H L A B27 T G M lines, the H L A molecule functions as restriction element in anti-viral responses. In addition, we could show that T lymphocytes of the transgenic animals respond to the same HLA-B27 restricted influenza peptide as is recognized by human influenza-specific, HLA-B27 restricted cytotoxic T cell lines. Key w o r d s : HLA-B27 transgenic mice, virus-specific cytotoxic T cell, peptide recognition.