Analysis of predicted CD8+ T cell epitopes from proteins encoded by the specific RD regions of Mycobacterium tuberculosis for vaccine development and specific diagnosis.
A number of regions designated as RD1-RD16 (region of difference) and encompassing 129 open reading frames have been identified between Mycobacterium tuberculosis and Mycobacterium bovis on the one hand and Bacillus Calmette-Guérin on the other. Identification of T cell epitopes from this set of proteins may serve to define candidate antigens with potentials in specific diagnosis and development of new vaccines against TB. All possible nonameric peptide sequences from proteins of these M. tuberculosis specific regions were analyzed in silico for the ability to bind to 33 alleles of class I HLA. These results reveal that of all RD proteins, a significant number of these peptides are predicted to be high-affinity HLA binders (T (1/2) >or= 100 min), irrespective of the length of the protein, and 67% of the peptides predicted to bind are mono-allelic in their binding. Pathogen peptides that could behave as self- or partially self-peptides in the host were eliminated using a comparative study with the human proteome, thus the number of peptides for analysis was reduced. The predicted epitopes can be tested experimentally for their inclusion in a potential vaccine against tuberculosis and specific diagnosis.
Wang
Jiuling
J
State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, 220 Handan Road, 200433, Shanghai, People's Republic of China.
Zhang
Hongmei
H
Wang
Honghai
H
D000483:Alleles; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology* / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*
D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D010455:Peptides; D032581:Tuberculosis Vaccines