T cell receptor and coreceptor CD8 alpha alpha bind peptide-MHC independently and with distinct kinetics

The T cell surface glycoprotein CD8 enhances T cell antigen recognition by binding to MHC class I molecules. We show that human CD8 alpha alpha binds to the MHC class I molecule HLA-A2 with an extremely low affinity (Kd simil ar to 0.2 mM at 37 degrees C) and with kinetics that are between 2 and 3 or ders of magnitude faster than reported for T cell receptor/peptide-MHC inte ractions. Furthermore, CD8 alpha alpha had no detectable effect on a T cell receptor (TCR) binding to the same peptide-MHC class I complex. These bind ing properties provide an explanation as to why the CD8/MHC class I interac tion is unable to initiate cell-cell adhesion and how it can enhance TCR re cognition without interfering with its specificity.