Generation and characterization of a clonotypic antibody specific for the T cell receptor of an arthritogenic T cell clone--studies in adjuvant arthritis.
Adjuvant Arthritis (AA) can be induced by passive transfer of a T cell clone (A2b) derived from arthritic rats, specific for Heat Shock Protein 60, HSP60 176-190. Furthermore, a crucial role for T cells with HSP60 176-190 specificity in AA was shown by induction of tolerance using HSP60 176-190 or by immunization with an altered peptide ligand based on the same sequence. To study clonal expansion of A2b-like T cells during AA and to determine their role in AA induction, we generated a clonotypic antibody, 16C4, specific for the TCR of the A2b T cell clone (TCR AV11S1/BV18). This antibody stained A2b T cells in flow cytometry experiments, induced proliferation of A2b cells when fixed on a solid support, and inhibited antigen-induced A2b proliferation when added in solution. A2b-like T cells were detected in a low frequency in lymphoid organs of arthritic rats. Thus, as in vivo administration of 16C4 did not inhibit AA, cells containing the determinant recognized by 16C4 are possibly not the sole contributors to AA development. Furthermore, epitope specific interventions by antigen administration may be possible even in cases where the epitope specific T cell clonotype is of low frequency.
Institute of Infectious Diseases and Immunology, Department of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
E A
EA
van Tienhoven
P G
PG
Steenbakkers
J G
JG
Veenstra
P J
PJ
van Kooten
M J
MJ
van der Cammen
C P
CP
Broeren
W
W
van Eden
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000737:chemistry / Q000627:therapeutic use; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control; D002460:Cell Line; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000032:analysis*; D005434:Flow Cytometry; D006825:Hybridomas; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell