Peptide epitopes - HIV and MBP related peptides

target7HIV-1 related peptide epitopes.
The chemokine receptor CCR5 that is utilized by infective human immunodeficiency virus 1 (HIV-1) variants R5 as co receptor for cell entry.
Interaction between the trimeric glycoprotein gp120-gp41 heterodimer structures on the HIV envelope with the host cell surface is a composite process aiming at binding and fusing the viral envelope to the plasma membrane of the target cell. Participation of the gp120 V3 domain (V3 loop) in the interaction with CCR5 is crucial in the binding process and cell entry. The third variable (V3) loop is an important region of gp120 for many biological processes, as it contains the highly conserved GPGR sequence and it represents the binding site for HIV-1 antibodies and for CCR5 and CXCR4 host cell co-receptors. The interaction of the principal neutralizing determinant (PND) V3 with the chemokine receptor CCR5 N-terminal region has been reported to be crucial for HIV-1 infection.
The solution structures of three HIV-1 gp120 V3 subtype B peptides have been determined (BMRB: 20015, 20019 & 20020) and their interaction with a non-sulfated N-terminal CCR5 peptide studied through NMR titration experiments suggesting that the V3 binding binding and selectivity is determined by simple electrostatic attraction mechanisms. It is found that the CCR5Nt-PND V3 interaction depends on the number of the positively charged V3 residues. This finding is in agreement with previous observations that increase in positive charge in the V3 sequence correlates with the interaction strength. Additionally, the NMR data demonstrate that the PND V3 and CCR5Nt peptide sequences have propensities for interaction even in the absence of sulfated tyrosines. Finally, this NMR study suggest that the PND V3 peptides retain the U-turn conformation (observed also in the crystal structures of gp120 complexes), independently of the CCR5 presence.

Myelin Basic Protein (MBP) peptide epitopes.
Multiple Sclerosis (MS) is a progressive demyelinating disease of the Central Nervous System (CNS), in which a coordinated attack of the immune system takes place against the myelin sheath. Although the antigenic components of myelin in MS have not been identified with certainty yet, Myelin Basic Protein (MBP) is believed to be one of the main candidate autoantigens and MBP87-99 is encephalitogenic in experimental autoimmune encephalomyelitis (EAE), the best studied animal model for MS. Analogues of immunodominant epitopes of these proteins (Altered Peptide Ligands - APLs) can induce or suppress EAE in rodents through the formation of trimolecular complex between the Major Histocompatibility Complex (MHC)-Peptide (Antigen)-T Cell Receptor (TCR) and the triggering of different immunological responses. Antagonism requires an APL to induce biochemical activity, which is inhibitory over the agonist-delivered signals. The solution models of three MBP87-99-related cyclic peptides and the native linear MBP83-99 peptide have been determined through 2D NMR spectroscopy (BMRB: 20062).