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Mtb-HAg can specifically induce \u03b3\u03b4 T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mtb-HAg extracted from the Mtb H37Ra strain was subjected to LC\u2012MS mass spectrometry. Twelve of the identified protein fractions were recombinantly expressed in<jats:italic>Escherichia coli<\/jats:italic>by genetic engineering technology using pET-28a as a plasmid and purified by Ni\u2013NTA agarose resin to stimulate peripheral blood mononuclear cells (PBMCs) from different healthy individuals. The proliferation of \u03b3\u03b4 T cells and major \u03b3\u03b4 T-cell subset types as well as the production of TNF-\u03b1 and IFN-\u03b3 were determined by flow cytometry. Their proliferating \u03b3\u03b4 T cells were isolated and purified using MACS separation columns, and Mtb H37Ra-infected THP-1 was co-cultured with isolated and purified \u03b3\u03b4 T cells to quantify<jats:italic>Mycobacterium<\/jats:italic>viability by counting CFUs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, Mtb-HAg from the attenuated Mtb H37Ra strain was analysed by LC\u2012MS mass spectrometry, and a total of 564 proteins were identified. Analysis of the identified protein fractions revealed that the major protein components included heat shock proteins and Mtb-specific antigenic proteins. Recombinant expression of 10 of these proteins in by<jats:italic>Escherichia coli<\/jats:italic>genetic engineering technology was used to successfully stimulate PBMCs from different healthy individuals, but 2 of the proteins, EsxJ and EsxA, were not expressed. Flow cytometry results showed that, compared with the IL-2 control, HspX, GroEL1, and GroES specifically induced \u03b3\u03b4 T-cell expansion, with V\u03b32\u03b42 T cells as the main subset, and the secretion of the antimicrobial cytokines TNF-\u03b1 and IFN-\u03b3. In contrast, HtpG, DnaK, GroEL2, HbhA, Mpt63, EsxB, and EsxN were unable to promote \u03b3\u03b4 T-cell proliferation and the secretion of TNF-\u03b1 and IFN-\u03b3. None of the above recombinant proteins were able to induce the secretion of TNF-\u03b1 and IFN-\u03b3 by \u03b1\u03b2 T cells. In addition, TNF-\u03b1, IFN-\u03b3-producing \u03b3\u03b4 T cells inhibit the growth of intracellular Mtb.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Activated \u03b3\u03b4 T cells induced by Mtb-HAg components HspX, GroES, GroEL1 to produce TNF-\u03b1, IFN-\u03b3 modulate macrophages to inhibit intracellular Mtb growth. These data lay the foundation for subsequent studies on the mechanism by which Mtb-HAg induces \u03b3\u03b4 T-cell proliferation in vitro, as well as the development of preventive and therapeutic vaccines and rapid diagnostic reagents.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s11658-024-00585-7","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T09:02:50Z","timestamp":1715590970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Analysis of the components of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) and its regulation of \u03b3\u03b4 T-cell function"],"prefix":"10.1186","volume":"29","author":[{"given":"Jing","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzheng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eldana","family":"Kaysar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyima","family":"Abdukayyum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangsheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqing","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9372-0386","authenticated-orcid":false,"given":"Tao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"585_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(22)00359-7","volume":"4","author":"S Bagcchi","year":"2023","unstructured":"Bagcchi S. 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