Immune recognition surface construction of Mycobacterium tuberculosis epitope-specific antibody responses in tuberculosis patients identified by peptide microarrays

- A different view of peptide microarray results relative to their biochemical characteristics is proposed for the first time.
- The amino acid sequences in antigenic epitopes dictate their polarity, affect processing and presentation to T cells, and antibody binding.
- The polarity of antigens may potentially influence the clinical relevance of ensuing adaptive immune responses in the host.
- The immune response landscape in a cohort provides a global view of the differential recognition of antigenic peptides by antibodies.
- 3D humoral immune landscape analysis allows the objective identification of complex antibody recognition patterns such as in tuberculosis.

SummaryBackgroundUnderstanding of humoral immune responses in tuberculosis (TB) is gaining interest, since B-cells and antibodies may be important in diagnosis as well as protective immune responses. High-content peptide microarrays (HCPM) are highly precise and reliable for gauging specific antibody responses to pathogens, as well as autoantigens.MethodsAn HCPM comprising epitopes spanning 154 proteins of Mycobacterium tuberculosis was used to gauge specific IgG antibody responses in sera of TB patients from Africa and South America. Open source software for general access to this method is provided.ResultsThe IgG response pattern of TB patients differs from that of healthy individuals, with the molecular complexity of the antigens influencing the strength of recognition. South American individuals with or without TB exhibited a generally stronger serum IgG response to the tested M. tuberculosis antigens compared to their African counterparts. Individual M. tuberculosis peptide targets were defined, segregating patients with TB from Africa versus those from South America.ConclusionsThese data reveal the heterogeneity of epitope-dependent humoral immune responses in TB patients, partly due to geographical setting. These findings expose a new avenue for mining clinically meaningful vaccine targets, diagnostic tools, and the development of immunotherapeutics in TB disease management or prevention.