T cell lines recognizing the 70-kD protein of U1 small nuclear ribonucleoprotein (U1snRNP).
In sera of patients with mixed connective tissue disease (MCTD) high titres of IgG autoantibodies to U1snRNP-specific proteins (70 kD, A, C) are found, suggesting an antigen-driven and T-cell-dependent process. In order to establish U1snRNP-specific T cell lines we cultured under various culture conditions mononuclear cells from MCTD patients and healthy donors with a highly purified UsnRNP preparation from HeLa cells. Nine T cell lines were established by limiting dilution cloning from two MCTD patients and five T cell lines from a healthy individual. All T cell lines expressed the TCR alpha beta/CD3 complex. Surprisingly, most of the T cells lines exhibited the CD8 phenotype. Irrespective of this phenotype, all T cell lines showed a proliferative response to an N-terminal part (aa 51-195) of recombinant U1-specific 70-kD protein. One CD8+ T cell clone exhibited cytotoxic activity against an autologous B cell line pulsed with snRNP or recombinant fragments (aa 51-95 and aa 51-88). Interestingly, two T cell lines proliferated in response to four recombinant polypeptides representing different parts of the U1snRNP 70-kD protein. Since regions of sequence homology are distributed over the 70-kD molecule, it is suggested that conserved motifs may be recognized by the T cell lines.
Fenning
S
S
Abteilung Rheumatologie und Klinische Immunologie, Chirurgische Universitätsklinik, Freiburg, Germany.
Wolff-Vorbeck
G
G
Hackl
W
W
Krawinkel
U
U
Lührmann
R
R
Northemann
W
W
Peter
H H
HH
Schlesier
M
M
D000328:Adult; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000276:immunology; D002999:Clone Cells; D003240:Connective Tissue Diseases / Q000276:immunology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D011994:Recombinant Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear