Antigen-specific T cells: analyses of the needles in the haystack

Abstract

Antigen binding to T cell receptors is a critical step in an immune response. Detection and characterization of rare populations of T cells enhances our ability to understand and treat disease

Figure 1. MHC Class I and MHC Class II Bind to Specific TCRs

MHC class I and MHC class II bind to specific TCRs on the surface of the MHC molecule that is facing you. The peptide is presented by the MHC to the TCR like a hotdog in a bun; the peptide typically constitutes approximately 15% and the MHC molecule constitutes approximately 85% of the surface that the TCR binds. (A) shows a molecular structure of the human MHC class I, HLA-A2, bound to a tumor antigen, MAGE-4 (Hillig et al. 2001). This structure is distinct from (B), which shows the human MHC class II molecule HLA-DR1 bound to a peptide derived from the Epstein–Barr virus gp42 protein (Mullen et al. 2002) in three ways. (1) The MHC class I peptide is shorter (average of nine amino acids versus 15 amino acids). (2) The ends of the peptide-binding grooves are closed in the MHC class I. (3) Although it is not evident in the structures shown, the binding groove from MHC class II is produced from two distinct molecules; the groove from MHC class I forms from one protein. The class I and II molecules can be found in animals from jawed vertebrates on up the evolutionary tree. (Figure produced with Cn3D version 4 from the National Center for Biotechnology Information.)