Brucella Peptide Cross-Reactive Major Histocompatibility Complex Class I Presentation Activates SIINFEKL-Specific T Cell Receptor-Expressing T Cells

spp. are intracellular pathogenic bacteria remarkable in their ability to escape immune surveillance and therefore inflict a state of chronic disease within the host. To enable further immune response studies, was engineered to express the well-characterized chicken ovalbumin (OVA). Surprisingly, we...

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Bibliographic Details
Published in:Infection and immunity 2018-07, Vol.86 (7)
Main Authors: Harms, Jerome S, Khan, Mike, Hall, Cherisse, Splitter, Gary A, Homan, E Jane, Bremel, Robert D, Smith, Judith A
Format: Article
Language:English
Subjects:
Animals
Antigen Presentation
Antigens, Bacterial - immunology
Brucella - immunology
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Cross Reactions
Histocompatibility Antigens Class I - immunology
Immune Evasion
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Ovalbumin - immunology
Peptide Fragments - immunology
Receptors, Antigen, T-Cell - immunology
T-Lymphocytes - immunology
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Summary:spp. are intracellular pathogenic bacteria remarkable in their ability to escape immune surveillance and therefore inflict a state of chronic disease within the host. To enable further immune response studies, was engineered to express the well-characterized chicken ovalbumin (OVA). Surprisingly, we found that CD8 T cells bearing T cell receptors (TCR) nominally specific for the OVA peptide SIINFEKL (OT-1) reacted to parental -infected targets as well as OVA-expressing variants in cytotoxicity assays. Furthermore, splenocytes from -immunized mice produced gamma interferon (IFN-γ) and exhibited cytotoxicity in response to SIINFEKL-pulsed target cells.To determine if the SIINFEKL-reactive OT-1 TCR could be cross-reacting to peptides, we searched the proteome using an algorithm to generate a list of near-neighbor nonamer peptides that would bind to H2K Selecting five peptide candidates, along with controls, we verified that several of these peptides mimicked SIINFEKL, resulting in T cell activation through the "SIINFEKL-specific" TCR. Activation was dependent on peptide concentration as well as sequence. Our results underscore the complexity and ubiquity of cross-reactivity in T cell recognition. This cross-reactivity may enable microbes such as to escape immune surveillance by presenting peptides similar to those of the host and may also lead to the activation of autoreactive T cells.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00281-18