We used five overlapping peptides comprising the N-terminal sequence 76-103 of the invariant chain (Ii) in mixed lymphocyte reaction (MLR) and antigen presentation system specific for tetanus toxoid (TT) to study their effects on human T cell proliferation. Invariant chain plays important role in the transport of major histocompatibility class II (MHC class II), and along with HLA-DM, the editing and charging of antigenic peptide onto the antigen binding groove of MHC class II.

Different effects on T cell proliferation distinguished peptides into two functional categories. CLIP (class II associated Ii protein, Ii 80-103) enhanced MLR, and augmented the TT-specific T cell proliferation when antigen presenting cells (APC) were prepulsed with TT, but decreased TT-specific proliferation when CLIP was added simultaneously with TT or before TT to APC. In contrast, the four shorter Ii peptides (from the N-terminal Ii 76-87 adjacent to CLIP) partially inhibited MLR. All these four Ii peptides augmented T cell proliferation in which TT and Ii peptides were added simultaneously to APC. All five Ii peptides inhibited antigen presentation when peptides were added to APC before TT.

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