Variations in the electrostatic landscape of class II human leukocyte antigen molecule induced by modifications in the myelin basic protein peptide: a theoretical approach.

The receptor-ligand interactions involved in the formation of the complex between Class II Major Histocompatibility Complex molecules and antigenic peptides, which are essential for establishing an adaptive immunological response, were analyzed in the Class II Human Leukocyte Antigen (HLA)--Myelin Basic Protein (MBP) peptide complex (HLA-DRbeta1*1501-MBP) using a multipolar molecular electrostatic potential approach. The Human Leukocyte Antigen--peptide complex system was divided into four pockets together with their respective peptide fragment and the corresponding occupying amino acid was replaced by each of the remaining 19 amino acids. Partial atomic charges were calculated by a quantum chemistry approach at the Hatree Fock/3-21*G level, to study the behavior of monopole, dipole and quadrupole electrostatic multipolar moments.

Allele effects in MHC-peptide interactions: a theoretical analysis of HLA-DRbeta1*0101-HA and HLA-DRbeta1*0401-HA complexes.

HLA-DRbeta1*0101-HA and HLA-DRbeta1*0401-HA complexes are studied and compared by means of their computationally derived multipolar moments and electrostatic potentials. Changes in electrostatic potential are associated with definite pocket interaction profiles. Thus, Pocket 1 projects itself as an anchoring pocket for both complexes, in accordance with experimental results.

A comparative study of MHC Class-II HLA-DRbeta1*0401-Col II and HLA-DRbeta1*0101-HA complexes: a theoretical point of view.

A study was performed on the HLA-DRbeta1*0401-collagen II peptide complex using the computation of electronic multipolar variables proposed by us previously. Furthermore, these results were compared with those obtained for the HLA-DRbeta1*0101-haemaglutinin peptide complex studied by us with the same tools, confirming that Pocket 1 for this new complex is also the most important pocket for the interaction between the presenting molecule and the presented peptide. The pocket hierarchy established for HLA-DRbeta1*0401 allele was P1 >> P9 approximately P7 > P6 > P4, whilst a P1 >> P4 > P9 approximately P7>P6 pocket hierarchy was found for HLA-DRbeta1*0101, showing how the relative importance of the pockets distinguishes the two alleles.