Conformational Constraints Involved in MHC Class I Restricted Antigen Presentation

Abstract

The realization that class I-restricted antigen presentation can be mimicked using synthetic peptides and the description of the class I three-dimensional structure has provided a basis with which to study the conformational constraints associated with cytotoxic T cell (CTL) recognition. Recent experiments have suggested that antigenic fragments can bind to class I molecules in extended conformations. This binding is dependent on the presence of predominant motif arrangements in the peptides which are likely to correspond to specific subsites within the class I binding cleft. Changes within this cleft can affect T cell receptor recognition by inhibiting peptide binding or by altering the conformation of the presented peptide. These changes can result in dramatic modifications in peripheral T cell recognition and in the thymic development of the T cells themselves. Consequently, class I molecules apparently control the T cell response via their effect on the binding and conformation of the presented peptide determinants.

Key Words:

• class I MHC
• cytotoxic T cells
• antigen presentation
• peptide conformation