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[Preprint]. 2024 Feb 29:2024.02.27.581790. [Version 1] doi: 10.1101/2024.02.27.581790

Treponema pallidum periplasmic and membrane proteins are recognized by circulating and skin CD4+ T cells

Tara B Reid, Charmie Godornes, Victoria L Campbell, Kerry J Laing, Lauren C Tantalo, Alloysius Gomez, Thepthara N Pholsena, Nicole A P Lieberman, Taylor M Krause, Victoria I Cegielski, Lauren A Culver, Nhi Nguyen, Denise Q Tong, Kelly L Hawley, Alexander L Greninger, Lorenzo Giacani, Caroline E Cameron, Julia C Dombrowski, Anna Wald, David M Koelle
PMCID: PMC10925203  PMID: 38464313

ABSTRACT

Background

Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum ( Tp )-specific CD4+ T cell responses to Tp infection. We hypothesized that Tp -specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment.

Methods

PBMC collected from 67 participants were screened by IFNγ ELISPOT response to Tp sonicate. Tp -reactive T cell lines from blood and skin were probed for responses to 88 recombinant Tp antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens.

Results

We detected CD4+ T cell responses to Tp sonicate ex vivo. Using Tp -reactive T cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, Tp -specific T cells persisted for at least 6 months in skin and 10 years in blood.

Conclusions

Tp infection elicits an antigen-specific CD4+ T cell response in blood and skin. Tp -specific CD4+ T cells persist as memory in both compartments long after curative therapy. The Tp antigenic targets we identified may be high priority vaccine candidates.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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