Concomitant multiepitope-directed targeting inhibits development of EAE associated with multiple pathogenic autoreactivities. (a) Multiantigen/epitope reactivity of hmTAP-reactive line T cells. Line T cells selected in vitro with hmTAP from LNCs of (C3H.SW × SJL/J)F₁ mice immunized with hmTAP/CFA were analyzed after four rounds of selection for their proliferative response to hmTAP, shMOG/E, rhMBP, shPLP215, and relevant encephalitogenic peptides (10 μg/ml). The proliferative response to PPD (5 μg/ml) was analyzed as a measure of specificity. (b) Tolerogenic administration of hmTAP completely abrogates the development in (C3H.SW × SJL/J)F₁ mice of EAE adoptively transferred by multispecific hmTAP-reactive line T cells. On day 0 (C3H.SW × SJL/J)F₁ mice were injected intravenously with the multispecific hmTAP-reactive line T cells (2 × 10⁶ cells). From day 1 to day 9 after T cell transfer the mice were injected daily intraperatoneally with PLP139-151 (150 μg), MOG37-52 (150 μg), or a mixture of both MOG35-55 and PLP139-151 (MOG + PLP; each 150 μg), or with hmTAP (100 μg), or with PBS alone (500 μl).