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

Abstract

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

MHC class II presentation of endogenously expressed antigens by transfected dendritic cells

“…4,[33][34][35] It is demonstrated that DC expressing Ii-OVA fusion cDNA with the OVA-specific MHC class I and II, or the MHC class II epitope only, were effective in eliciting potent MHC class II-restricted T cell responses in DC/T cell cocultures in vitro. Interestingly, efficient MHC class I presentation was also achieved although the Ii fusion targets the antigen to the MHC class II processing pathway.…”

“…PCR primers were designed to introduce DraIII restriction sites at either end of the fragments. PCR fragments were inserted into the DraIII site of pEXV3-Ii31 34 and Ii-OVA fusions were then cloned into EcoRI of pcDNA3 thereby generating pcDNA3-Ii-OVA.II and pcDNA3-Ii-OVA.I+II plasmid, respectively. The integrity of the Ii-OVA fusions was confirmed by DNA sequencing.…”

The Th1 immune response against HIV‐1 Gag p24‐derived peptides in mice expressing HLA‐A02.01 and HLA‐DR1

“…We therefore sought to identify, among the seven structurally conserved HIV-1 p24-derived CD4 + T cell epitopes, those that would best support the induction of potent cytolytic responses. To compare the Th1 helper potential of these epitopes, they were introduced separately in the C-terminal portion of the mouse invariant chain [18]. Other lysosomal molecules (LAMP, LIMP) have been used as cargo molecules to sort antigens to lysosomal compartments, but with mixed success [19].…”

Transfection of dendritic cells (DCs) with the CIITA gene: increase in immunostimulatory activity of DCs

“…Antigenic peptides bind to class II dimers and are presented on the cell surface of APC to CD4 T cells. 15 Co -players of antigen processing are the invariant chain (li ) , MHC encoded DM and DO molecules, and certain proteases. 16 ± 18 The transactivator CIITA (a non ±DNA -binding transactivator, which regulates the expression of MHC class II, HLA -DM, and invariant chain ) behaves as a master controller of constitutive and inducible MHC class II gene activation.…”