THE TETRAMER MODEL - A NEW VIEW OF CLASS-II MHC MOLECULES IN ANTIGENIC PRESENTATION TO T-CELLS

Crystallographic studies suggest a plausible divalent interaction betw een T-cell receptor (TCR) and MHC class II molecules. In addition, bio chemical data suggest that these divalent MHC molecules are preformed at the membrane of the antigen-presenting cell. The tetramer model is based on these preformed tetrameric class II molecules that can be loa ded with identical or different peptides in their two grooves. This en ables divalent class II molecules to deliver two different messages to T cell: 1) a two-peptide message, in which the tetramer with two iden tical peptides is able to cross-link two TCRs triggering full activati on of a T cell. At the thymic level we propose that this message induc es negative selection; or 2) a one-peptide message: only one of the pe ptides loaded in the class II tetramer is able to interact with that T CR. This message would be involved in triggering partial activation ph enomena in mature lymphocytes, whereas in thymocytes this message woul d mediate positive selection. Since high concentrations of a peptide w ould favor the load of tetramers with identical peptides, the tetramer could therefore be viewed as a quantitative-qualitative transducer th at would trigger different responses depending on the concentration of antigenic peptides.