Topology and affinity of T-cell receptor mediated recognition of peptide-MHC complexes

Significant progress has been made on several long-standing issues regarding T-cell receptor mediated recognition of antigen-MHC complexes. For one, early data suggest that the affinity of the T-cell receptor for the peptide-MHC complex is extremely low, with a KD of approximately 10(-4)-10(-5)M, much weaker than most antibody-antigen interactions. The fact that this affinity is lower than that of some T-cell adhesion molecules for their ligands could have important implications for immune surveillance. A second area of interest is the topology of T-cell receptor recognition; evidence of direct contact between the third complementarity determining region of the T-cell receptor and peptide determinants has been obtained. In addition, the orientation of the T-cell receptor with respect to several antigen-MHC complexes has been predicted. They suggest that whereas most or all peptides seem to bind in the same orientation in both class I and class II MHC molecules, the orientation of the T-cell receptor over the peptide-MHC complex may not be fixed.