Work

Identification of candidate HLA-E binding peptides from Mycobacterium tuberculosis using phage secretome library screening and computational modeling

Year: 2026

Type: article

Abstract: Background Mycobacterium tuberculosis ( Mtb ) remains a primary global health challenge, particularly in HIV-co-infected populations where viral Nef-mediated downregulation of classical MHC-I molecules impairs T-cell immunity. Conversely, the non-classical MHC-Ib molecule, HLA-E, is resistant to Nef-mediated evasion, representing an attractive, non-polymorphic pathway for investigating potential Mtb -specific CD8 + T-cell activation targets. Methods This study utilized an exploratory in vitro screening and in silico modeling framework to identify candidate HLA-E-binding Mtb peptides. Candidate ligands were screened by biopanning an Mtb F15/LAM4/KZN phage secretome library against immobilized recombinant HLA-E*01:03. Identified peptides were characterized via DNA sequencing, and their predicted structural–mechanical interactions were evaluated using molecular docking and normal mode analysis (NMA). Results Phage selection yielded distinct Mtb -derived peptide fragments, including components from known immunogenic antigens Rv1980c (Mpt64) and Rv2875 (Mpt70), alongside conserved hypothetical proteins such as Rv1566c. Structural profiling predicted groove-directed anchoring within the modeled HLA-E binding cleft, displaying a spatial preference for pockets E and F. Computational molecular scoring prioritized favorable candidates (e.g., Rv2972c at −87.49 kcal/mol), while NMA indicated that these prioritized Mtb peptides possess a higher degree of predicted conformational plasticity (eigenvalues as low as 9.13 × 10 -6 ) compared to the rigid Mtb44 baseline (1.37 × 10 –4 ). Conclusion These findings map an exploratory Mtb peptide repertoire demonstrating computational feasibility for flexible HLA-E groove accommodation. By providing a structural foundation for candidate peptide prioritization, these results lay the groundwork for future investigations into unconventional CD8 + T-cell activation and the rational design of next-generation TB vaccines tailored for high-burden TB/HIV co-infection settings.

Source: Frontiers in Cellular and Infection Microbiology

DOI: 10.3389/fcimb.2026.1724374

Authors: Nkanyezi Masondo, Michelle Lucille Gordon, Thamsanqa Emmanuel Chiliza

Institution: University of KwaZulu-Natal

Language: English

Topic: vaccines and immunoinformatics approaches

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801