Ised, Kd Cattle_A20 B_2705 B7, Cw_0401 A_0201 B_3801 Kd B
Ised, Kd Cattle_A20 B_2705 B7, Cw_0401 A_0201 B_3801 Kd B7 B_2702, B_2705 B62, B_2705, B_3902 A_3101, B_2705, Cattle_A20 A_0201 B_2705, Cattle_A20 B_2705, Cattle_A20 B_2705, Cattle_AVpr. Of the 96 residues, 62 (65 ) have been shown to be associated with experimentally defined CTL epitopes. The data presented in Table 16 show that there are polymorphisms with respect to the experimentally verified CTL epitopes. The presence of variant amino acids at distinct locations within the epitope is likely to impact the CTL epitope. Further, we have also evaluated the effect of Vpr polymorphisms on CTL epitopes using the bioinformatics approach by calculating the estimate of half time of disassociation of the molecule containing the epitope. Such an analysis predicted several CTL epitopes all over Vpr including the C-terminus with respect to specific HLA class 1 molecules. The detailed analysis was carried out for different HLA alleles (HLA-A2, Cw-4, HLA-B7 and HLAB2705) involving a total of 12 epitopes. The polymorphisms have also been analyzed for three predicted epitopes corresponding to residues 18?6, 38?6, and 66?4. The substitution of the variant amino acids for the residues comprising the epitope resulted in a drastic reduction in the value corresponding to the half time of the disassociation of the molecule containing the epitope. It should, however be noted that additional in vitro binding studies are necessary to confirm the predicted values. Based on the data presented here, the amino acid polymorphisms noted in Vpr have the potential to contribute to the escape of the virus along with the epitopes BMS-214662 site present in other HIV-1 proteins [30]. It is also likely that the information regarding PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28250575 the polymorphisms PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26795252 at the CTL epitope will provide an opportunity to create an epitope-based vaccine that will exert control over viral isolates from different parts of the world. It is important to mention that the extensive HLA-associated amino acid polymorphismsnoted here may also impact on the structure/function of Vpr and fitness of the virus [10,81-85]. The biological sources used for generating the sequence information of vpr include tissues from infected individuals, plasma viral RNA, and cloned viral DNA. For this reason, the Vpr sequences considered here for the analysis may be derived from both infectious and non-infectious viral genomes. Hence, there is a possibility that the amino acid polymorphisms noted here may or may not have a chance to be acted upon by CTL and T-helper cell pressures. It is known that amino acids in the proximal region of the epitope can also influence their immunogenic potential. The amino acid polymorphisms noted in the putative CTL epitopes can have an effect at a single and/or multiple levels in the generation of immune response: i) The mutations may eliminate the binding of the peptide to the appropriate HLA molecule, which will be presented on the cell surface. ii) Mutations may also disrupt the interaction with the Tcell receptors. iii) Mutations may disrupt the intracellular processing of the peptides. This results in the escape of the cells expressing the viral proteins from the surveillance of CD8+ T cells. The variant amino acids present in the proximal or far away from the epitope could influence through interference with the processing of the peptide from the protein. With regard to the latter, the variant amino acids may be either independent or compensatory in relation to changes in specific residues of Vpr.