Abstract
Are the extracellular IgV and IgC domains of butyrophilin 3A1 required for prenyl pyrophosphate stimulation of human Vγ2Vδ2 T cells?
The Journal of immunology (1950), Vol.196(1_Supplement), pp.116-116.3
05/01/2016
DOI: 10.4049/jimmunol.196.Supp.116.3
Abstract
Abstract Vγ2Vδ2 T cells play important roles in human immunity to pathogens and in cancer immunotherapy by responding to isoprenoid metabolites such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) and isopentenyl pyrophosphate (IPP). The immunoglobulin superfamily protein, butyrophilin 3A1 (BTN3A1), is required for prenyl pyrophosphate stimulation. Our mutational studies and the work of others has shown that HMBPP and IPP compounds are not antigens but instead are sensed molecules that bind to the intracellular B30.2 domain of BTN3A1. How this binding is detected by the Vγ2Vδ2 TCR is unclear. One possibility is that HMBPP binding alters the conformation and/or distribution of the extracellular domains (ECD) of the BTN3A1 dimer allowing direct binding to the Vγ2Vδ2 TCR or to another molecule that binds the Vγ2Vδ2 TCR. Alternatively, the Vγ2Vδ2 TCR could bind to a molecule that is recruited by the intracellular B30.2 domain upon HMBPP binding. To distinguish between these mechanisms, we mutagenized 32 residues on the surfaces of the IgV and IgC domains of BTN3A1 to alanine and tested the mutant proteins for their ability to mediate prenyl pyrophosphate stimulation of Vγ2Vδ2 T cells. Mutagenesis of residues in the IgV and IgC domains had no effect whereas mutagenesis of the B30.2 binding site abrogated Vγ2Vδ2 T cell responses to HMBPP. Therefore, these findings do not support direct binding to the Vγ2Vδ2 TCR (or to another protein) by the ECD of BTN3A1. Instead, Vγ2Vδ2 TCR recognition may be to a protein recruited to the B30.2 domain upon HMBPP binding. Identification of this second protein will help clarify the puzzling process of human Vγ2Vδ2 T cell receptor recognition.
Details
- Title: Subtitle
- Are the extracellular IgV and IgC domains of butyrophilin 3A1 required for prenyl pyrophosphate stimulation of human Vγ2Vδ2 T cells?
- Creators
- Craig T MoritaHong Wang
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.196(1_Supplement), pp.116-116.3
- DOI
- 10.4049/jimmunol.196.Supp.116.3
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2016
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984363306202771
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