Nasal application of a naturally processed and presented T cell epitope derived from TCR AV11 protects against adjuvant arthritis

Abstract

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.

Vaccination against autoimmune diseases moves closer to the clinic

“…15 In follow-up studies, it was shown that TcR peptides can have the capacity to protect against arthritis in the experimental model upon in vivo nasal administration. 16 Although with the relatively recent revival of interest in T cell regulation the focus of research has been on therapeutic applications of Treg, also the regulatory B cell or the Breg may have the potential for tolerance induction. Although Breg was known to downregulate immune responses by secretion of IL-10 and IL-35, the origin of Bregs had remained a bit unclear.…”