NDLI: Antigen Specific CD4+ and CD8+ T Cell Recognition During Mycobacterium Tuberculosis Infection

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Antigen Specific CD4+ and CD8+ T Cell Recognition During Mycobacterium Tuberculosis Infection

Content Provider	Semantic Scholar
Author	Yang, Jason D.
Copyright Year	2018
Abstract	Mycobacterium tuberculosis (Mtb) causes human tuberculosis, and more people die of it than of any other pathogen in the world. Immunodominant antigens elicit the large majority of T cells during an infection, making them logical vaccine candidates. Yet, it is still unknown whether these immunodominant antigenspecific T cells recognize Mtb-infected cells. Two immunodominant antigens, TB10.4 and Ag85b, have been incorporated into vaccine strategies. Surprisingly, mice vaccinated with TB10.4 generate TB10.4-specific memory CD8 T cells but do not lead to additional protection compared to unvaccinated mice during TB. Ag85b-specific CD4 T cells are also generated during vaccination, but the literature on whether these cells recognize Mtb-infected cells is also inconsistent. We demonstrate that TB10.4-specific CD8 T cells do not recognize Mtbinfected cells. However, under the same conditions, Ag85b-specific CD4 T cells recognize Mtb-infected macrophages and inhibit bacterial growth. In contrast, polyclonal CD4 and CD8 T cells from the lungs of infected mice can specifically recognize Mtb-infected macrophages, suggesting macrophages present antigens other than the immunodominant TB10.4. The antigen location may also be critical for presentation to CD8 T cells, and live Mtb may inhibit antigen presentation of TB10.4. Finally, we propose that TB10.4 is a decoy antigen as it elicits a robust CD8 T cell response that poorly recognizes Mtb-infected macrophages, allowing Mtb to evade host immunity.
File Format	PDF HTM / HTML
DOI	10.13028/M27M3N
Alternate Webpage(s)	https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1974&context=gsbs_diss
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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