Kinetic and thermodynamic studies of the interaction between activating and inhibitory LY49 Natural Killer receptors and MHC-I molecules

ROMASANTA P; SARRATEA B; CURTO L; NOLI TRUANT S; FERNANDEZ LYNCH MJ; ANTONOGLOU B; TODONE M; DE MARZI MC; DELFINO JM; FERNANDEZ M; MALCHIODI E

Mar del Plata, Buenos Aires

Congreso; LIX Reunión Científica Anual, SAIC, LXII Reunión Anual SAI; 2014

Sociedad Argentina de Inmunología-Sociedad Argentina de Investigación Clínica

Pagina 141 del adjunto The interactions between mice Natural Killer (NK) cell receptors Ly49 and the endogenous mayor histocompatibility complex type I (MHC-I) ligands are of capital importance for the regulation of viral infections and tumorigenic processes. The interactions Ly49H/H-2Dd, Ly49I/H-2Dd and Ly49G/H-2Dk were particularly studied. They embrace the structural heterogeneity of Ly49 and interact with different MHC-I alleles. Thermodynamic and kinetic experiments were carried out in order to elucidate the Ly49/MHC-I binding mechanism. Combining surface plasmon resonance (SPR), fluorescence anisotropy (FA), and far-UV circular dichroism (CD), an identical and independent binding sites model was determined, where the MHC-I binds to Ly49 with a ~106 M-1 binding constant. There is no evidence of a strong positive cooperativity such as seen with the interactions between Ly49 and m157, a murine cytomegalovirus decoy molecule. The rate-limiting step of the overall mechanism is the diffusion of the molecules. Using SPR we also studied the Ly49G/MHC-I peptide insensitivity, and identified for the first time interactions between activating Ly49H and endogenous ligands in the absence of viral molecules.