T cell receptor clonotypes in skin lesions from patients with systemic lupus erythematosus

Systemic lupus erythematosus is an autoimmune disease characterized by the presence of autoantibodies and by lymphocytic infiltration into lesions at several sites such as skin, kidney, and other organs. Immunohistologic studies have clarified that the majority of lymphocytes in the skin are CD4(+) alpha beta T cells. In the present work, to clarify the pathologic role of T cells in the skin of systemic lupus erythematosus patients, we analyzed T cell receptor (TCR) clonotypes of T cells infiltrating into skin lesions. TCR V beta gene transcripts from T cells from discoid lesions of the skin and peripheral blood lymphocytes of four systemic lupus erythematosus patients were amplified by reverse transcriptase polymerase chain reaction. Southern blot analysis of polymerase chain reaction product demonstrated the heterogeneous TCR V beta repertoire of T cells in the skin of systemic lupus erythematosus. Single-strand conformation polymorphism analysis showed several distinct bands for smears of most TCR V beta genes from T cells infiltrating the skid, whereas smears with few bands were found for all TCR V beta genes from peripheral blood lymphocytes of the same patients. The number of bands encoding each TCR V beta gene from the skin was significantly higher compared with peripheral blood lymphocytes. Sequencing analysis showed a Leucine-X-Glycine amino acid motif at position 96-98 in the CPR3 region at the frequency of 23-24% in skin-accumulated T cells from two patients, whereas the frequency of this motif in peripheral T cells was only 0-3%, indicating limited T cell epitopes. In conclusion, T cells infiltrating into the skin of systemic lupus erythematosus patients might recognize restricted T cell epitopes on autoantigens and trigger the autoimmune reaction in skin lesions.