Cooperative Recognition of MHC Class II:Peptide Complexes by the T Cell Receptor and CD4

Abstract

Since the T cell receptor (TCR) was cloned almost twelve years ago, significant attention has been directed towards understanding the mechanism by which it recognizes its ligand.1,2 For immunoglobulin (Ig), antigen recognition would appear theoretically simple as it invariably binds a single molecule. However, the TCR cannot recognize native proteins and instead foreign antigens must first be processed into short peptides and bound to products of the major histocompatibility complex (MHC) class I or class II loci for presentation to T cells.3–8 Clearly, the TCR must be able to discriminate between its specific ligand combination, and irrelevant peptides bound to the appropriate MHC restriction element or the appropriate peptide bound to another MHC molecule. While this central tenet is the foundation of self:nonself discrimination,9–11 it is unclear whether the TCR can functionally discriminate between MHC molecules and peptide or whether, like immunoglobulin, it recognizes this complex as a single entity.