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Human immune response to Mycobacterium tuberculosis antigens
D V Havlir1, R S Wallis, W H Boom
1Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Infection and Immunity
|February 1, 1991
Summary
Healthy individuals exposed to tuberculosis (TB) mount a strong cell-mediated immune response to specific Mycobacterium tuberculosis antigens, particularly antigen 6/alpha antigen and HSP60. This study identifies key antigens driving immune responses in TB-resistant individuals, crucial for vaccine development.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Cell-mediated immunity is crucial for protection against Mycobacterium tuberculosis (M.tb).
- Understanding immune responses in healthy, tuberculin-positive individuals offers insights into natural resistance to tuberculosis.
- Identifying immunodominant antigens is key for developing effective TB vaccines and diagnostics.
Purpose of the Study:
- To compare the targets of cell-mediated immune responses in healthy tuberculin-positive individuals, tuberculosis patients, and tuberculin-negative persons.
- To identify specific M.tb antigens that elicit blastogenic responses in lymphocytes.
- To investigate the role of known proteins like antigen 6/alpha antigen, HSP60, and HSP70 in these responses.
Main Methods:
- T-cell Western blotting (immunoblotting) was used to analyze M.tb culture filtrate antigens.
- Lymphocyte blastogenic responses ([3H]thymidine incorporation) were measured against purified antigens and fractions.
- Antibody reactivity to M.tb culture filtrate was assessed in patient and control sera.
Main Results:
- Healthy tuberculin reactors showed significant T-cell blastogenic activity against seven M.tb antigen fractions (30, 37, 44, 57, 64, 71, and 88 kDa).
- Fractions at 30, 64, and 71 kDa corresponded to antigen 6/alpha antigen, HSP60, and HSP70, respectively.
- Lymphocytes from healthy reactors responded robustly to purified antigen 6/alpha antigen and moderately to HSP60.
- Tuberculous patients showed higher antibody titers to M.tb filtrate, inversely correlating with blastogenic responses.
Conclusions:
- Antigen 6/alpha antigen and HSP60 are significant stimulators of cell-mediated immunity in healthy individuals with prior M.tb exposure.
- The identified immunodominant antigens warrant further investigation for their potential in TB vaccine development.
- Differential immune responses highlight distinct immunological profiles between healthy reactors and active TB patients.