Nasal application of a naturally processed and presented T cell epitope derived from TCR AV11 protects against adjuvant arthritis.
Reactivity towards TCR peptides plays an important role in the regulation of several experimental autoimmune diseases. In a previous paper, we showed the TCRAV11 usage by an arthritogenic T cell clone isolated from a rat with adjuvant arthritis (AA). Moreover, we identified three immunogenic peptides in AV11: AV11 24-40, 41-55 and 66-80. In the present study, we show that T cells directed towards all three epitopes are part of the immune repertoire. The strongest delayed-type hypersensitivity (DTH) reaction was observed against the peptide derived from the third framework region, peptide AV11 66-80. DTH reactions to this peptide were detectable in naive rats and increased significantly after AA induction. Interestingly, modulation of the AV11 66-80 T cell response by nasal AV11 66-80 administration resulted in reduced DTH responses and in a strong inhibition of AA. These findings suggest that during the natural course of AA, T cells directed towards the third framework region of AV11 do not have a disease regulatory function, but instead play a role in the deterioration of AA.
van Tienhoven
E A
EA
Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, PO Box 80165, Yalelaan 1, 3508 TD Utrecht, The Netherlands.
Broeren
C P
CP
Noordzij
A
A
Wagenaar
J P
JP
van Eden
W
W
Wauben
M H
MH
D000281:Administration, Intranasal; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D018450:Disease Progression; D000939:Epitopes / Q000008:administration & dosage; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000008:administration & dosage* / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology; D014611:Vaccination
D000939:Epitopes; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell