The diagnostic potential of MPT63‐derived HLA‐A*0201‐restricted CD8⁺T‐cell epitopes for active pulmonary tuberculosis

Abstract

MPT63 protein is found only in Mycobacterium tuberculosis complex, including M. tuberculosis and M. bovis. Detection of MPT63-specific IFN-g-secreting T cells could be useful for the diagnosis of tuberculosis (TB) diseases. In the present study, the HLA-A Ã 0201 restriction of ten predicted MPT63-derived CD8 + T-cell epitopes was assessed on the basis of T2 cell line and HLA-A Ã 0201 transgenic mice. The diagnostic potential of immunogenic peptides in active pulmonary TB patients was evaluated using an IFN-g enzyme-linked immunospot assay. It was found that five peptides bound to HLA-A Ã 0201 with high affinity, whereas the remaining peptides exhibited low affinity for HLA-A Ã 0201. Five immunogenic peptides (MPT63 18-26 , MPT63 29-37 , MPT63 20-28 , MPT63 5-14 and MPT63 [10][11][12][13][14][15][16][17][18][19] ) elicited large numbers of cytotoxic IFN-g-secreting T cells in HLA-A Ã 0201 transgenic mice. Each of the five immunogenic peptides was recognized by peripheral blood mononuclear cells from 45% to 73% of 40 HLA-A Ã 0201 positive TB patients. The total diagnostic sensitivity of the five immunogenic peptides was higher than that of a T-SPOT.TB assay (based on ESAT-6 and CFP-10) (93% versus 90%). It is noticeable that the diagnostic sensitivity of the combination of five immunogenic peptides and T-SPOT.TB assay reached 100%. These MPT63-derived HLA-A Ã 0201-restricted CD8 + T-cell epitopes would likely contribute to the immunological diagnosis of M. tuberculosis infection and may provide the components for designing an effective TB vaccine. Key words CD8+ T-cell epitope, HLA-A Ã 0201, MPT63, Mycobacterium tuberculosis.Tuberculosis, which is caused by the intracellular pathogen M. tuberculosis, is still a major global health problem, especially in developing countries (1). M. tuberculosis can infect all kinds of tissues or organs (especially lung) and causes TB-related diseases. Although the BCG vaccine is used worldwide, it is only currently effective against severe childhood forms of TB, its efficacy in adults being controversial (2). The increasing emergence of multidrug-resistant strains of M. tuberculosis has exacerbated the issue of TB. Currently, fast and precise diagnosis of M. tuberculosis infection is critical for the treatment of TB-related diseases. TSTs and detection of acid-fast bacilli in sputum samples are the conventional methods for List of Abbreviations: aa, amino acid; BCG, M. bovis Bacilli Calmette-Gu erin; CFP-10, 10 kDa culture filtrate antigen; ELISPOT, enzyme-linked immunospot; ESAT-6, 6 kDa early secretory antigenic target; E:T ratio, effector to target cell ratio; FI, fluorescence index; LDH, lactate dehydrogenase; LNC, lymph node cell; MFI, mean fluorescence intensity; PBMC, peripheral blood mononuclear cell; PPD, purified protein derivative; SFC, spot-forming cell; SMC, splenic mononuclear cell; TB, tuberculosis; TST, tuberculin skin test.

Cloning and Expression of Recombinant Protein MPT63 of Mycobacterium tuberculosis Indonesian Isolate as Serodiagnostic Latent Tuberculosis

“…MPT63 is a secreted protein, specific for mycobacteria, and immunogenic [9]. MPT63 is produced by the M. tuberculosis complex and does not have serological cross-reactivity between MPT63 and proteins from other mycobacterial species, so MPT 63 is a candidate for the specific diagnosis of complex M. tuberculosis and vaccines [10].…”

Nanoparticle Induced Conformational Switch Between α-Helix and β-Sheet Attenuates Immunogenic Response of MPT63

“…First, MPT63 is a target against TB, which has been shown to have immunogenic properties . Efforts are underway to develop NP-conjugated MPT63 as a therapeutic strategy against TB . There are two types of immune response: one is protective immunity also known as Th-1 response and the other is suppressive immunity or Th-2 response.…”

“…11 Efforts are underway to develop NP-conjugated MPT63 as a therapeutic strategy against TB. 12 There are two types of immune response: one is protective immunity also known as Th-1 response and the other is suppressive immunity or Th-2 response. Th-1 response helps the host to restore immunity against any upcoming pathogenic infection or immune suppression, whereas increased Th-2 response is associated with a diseased condition and pathogenesis.…”