T cell receptor and coreceptor CD8 alphaalpha bind peptide-MHC independently and with distinct kinetics
Wyer JR, Willcox BE, Gao GF, Gerth UC, Davis SJ, Bell JI, van der Merwe PA, Jakobsen BK. (1999), Immunity. 10, 219-25
The T cell surface glycoprotein CD8 enhances T cell antigen recognition by binding to MHC class I molecules. We show that human CD8 alphaalpha binds to the MHC class I molecule HLA-A2 with an extremely low affinity (Kd approximately 0.2 mM at 37 degrees C) and with kinetics that are between 2 and 3 orders of magnitude faster than reported for T cell receptor/peptide-MHC interactions. Furthermore, CD8 alphaalpha had no detectable effect on a T cell receptor (TCR) binding to the same peptide-MHC class I complex. These binding properties provide an explanation as to why the CD8/MHC class I interaction is unable to initiate cell-cell adhesion and how it can enhance TCR recognition without interfering with its specificity..
Key figure: The Affinity of CD8αα Binding to HLA-A2
(A) CD8αα was injected at the indicated concentrations for 30 s through flow cells with ∼8000 RUs of either HLA-A2-flu (solid trace) or the control protein OX68 (dotted trace) immobilized. HLA-A2-flu was coupled via biotinylated β2-microglobulin. The amount of CD8αα that bound HLA-A2-flu at each concentration was calculated as the difference between the responses at equilibrium in the HLA-A2-flu and control flow cells and is plotted in (B). (C) A similar experiment was performed at 37°C using HLA-A2-HY (∼2400 RU) coupled via biotinylated heavy chain and OX68 (∼4000 RU) as a control protein. In (B) and (C) the solid lines in the main plots represent nonlinear fits of the Langmuir binding isotherm to the data. These yielded Kd values of 156 and 205 μM, respectively. The insets show Scatchard transformations of the same data; the Kd values shown were obtained from the slopes by linear regression (Kd = −1/slope). These experiments were performed at a flow-rate of 10 μl × min−1.