C-terminal extension of the MHC class II-associated invariant chain by an antigenic sequence triggers activation of naive T cells.

In vitro and in vivo activation of T cells was investigated with invariant chain-antigen fusion protein. The CD4 T cell epitope amino acid 52-61 of hen egg lysozyme (HEL) was attached to the C-terminal end of invariant chain (Ii). Expression of this recombinant Ii HEL directs the T cell epitope to the class II processing pathway. Class II molecules of transfected antigen presenting cells (APC) are charged with this HEL epitope. The endogenously provided epitope competes with processing and presentation of exogenously added antigen. APC expressing recombinant Ii HEL stimulate a maximal IL-2 response of HEL-specific T hybridoma cells. Nonprofessional APC expressing recombinant Ii HEL and H2-Ak are also able to activate naive T cells from 3A9 TCR transgenic mice, a result not achieved with peptide pulsed APC. To elicit an in vivo immune response dendritic cells (DC) were transfected with rIi HEL cDNA: following immunization of CBA mice with transfected DC, a primary T cell response against the HEL epitope was induced. Thus the procedure described here could be used to introduce antigens into the class II processing pathway and to elicit T cell activation both in vitro and in vivo.