Abstract
Melanomas represent the most resistant form of cancer. If detected early, a cure is possible with the conventional therapies, while metastatic forms are almost resistant to conventional therapies. A new area i.e. immune based therapy shows promise of cytolytic activity against tumor cells. Production of antibodies against the antigenic epitopes present in the melanoma is the main basis of this immune based therapy. Production of T cell response against the tumor cells has been seen by synthetic antigenic epitopes. The antigenic nonameric peptide epitope of tyrosinase (192-200) with the sequence S1EIWR5DIDF9 causes significant induction of the T cell response in melanoma patients. In realm of the significance of this peptide, a solution state NMR structure of 192-200 amino acid section of tyrosinase has been investigated, to assimilate the relationship between the antigenicity and the conformation of the peptide. NMR studies were carried out in H2O:D2O (95:5) and DMSO-d6 solvents. Molecular dynamics simulations with NMR constraints were carried out using the GROMACS v .4.6.5 package. The results suggest the prevalence of a β-sheet structure both in H2O as well as in DMSO-d6.
Highlights
Melanoma is a malignant tumor of the melanocytes which are pigment producing cells in the skin [1]
These antigens range from the 3D structures of small molecules that are identified by antibodies, to amino acid sequences which are recognized by CTLs
Among the cells expressing tyrosinase endogenous peptide subtypes of HLA-B44, the HLA-B*4403 subtype is lysed by the anti-MZ2-C CTL clone, whereas those of the B*4402 subtype undergo very insignificant lysis
Summary
Melanoma is a malignant tumor of the melanocytes which are pigment producing cells in the skin [1]. In tumor rejection the important requirement is the ability of the immune system to recognize TAA, and to elicit an immune response against the tumor cells [7,8] These antigens range from the 3D structures of small molecules that are identified by antibodies, to amino acid sequences which are recognized by CTLs. Induction of T cell mediated immune response is activated by the following two steps. Among the cells expressing tyrosinase endogenous peptide subtypes of HLA-B44, the HLA-B*4403 subtype is lysed by the anti-MZ2-C (an antigen produced by the melanoma patients) CTL clone, whereas those of the B*4402 subtype undergo very insignificant lysis. They differ by a single Asp (B*4402) to Leu (B*4403) substitution in position 156 of the α2-domain [13]. That different conformations of the peptide in the B*4402 and B*4403
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