Abstract Details
8/22/2022 | 2:15 PM - 2:40 PM | Confederation II/III
Prediction of Optimal Epitopes for Cytomegalovirus-specific CD8-T cells
Cytomegalovirus (CMV) causes severe disease and CD8 T cells are critical for viral control, but protective epitopes are elusive. We used a composite algorithm to identify CD8 T cell-stimulating peptides and have low risk of viral escape or immunopathology. Using CMV PRA4 from a congenital infection, favorable epitopes were identified by: 1) antigen-presenting cell processing, 2) MHC-peptide binding affinity (BA), 3) BA after point mutations (BA-M) as a measure of immune escape 4) regions of high protein disorder where mutation may lead to escape, and 5) cross-reactivity with human proteins as a marker of immunopathology. Sixty-three proteins recognized by CD8 T cells (Sylwester 2005) were examined. Efficient processing (top 20%) and high BA (IC50 ?500nM) for common MHC alleles (n=69) yielded 18,035 peptides. Point mutations led to reduced BA-M. Regions of low disorder were associated with high BA, suggesting high barrier to escape. Cross-reactivity was low for most peptides. Composite yielded 1,968 predicted favorable epitopes, of which 60% were not previously identified. This approach may narrow targets of this large DNA virus when designing immune-based CMV interventions.
- Identify CD8 T cell-stimulating peptides and have low risk of viral escape or immunopathology
- Investigate with a broad whole-genome approach in a clinical strain of CMV
- Hypothesize potential targets for immune-based CMV interventions
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Bennett Vogt (POC-Point of Contact,Primary Presenter), bennett.vogt@umassmed.edu;
Third-year medical student at the University of Massachusetts Chan Medical School, bioinformatics research on congenital CMV. Harvard undergrad degree in chemical and physical biology specializing in protein structure prediction. Seeking combined medicine-pediatric residency programs.
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ASHA DISCLOSURE: Financial - No relevant financial relationship exists. Nonfinancial - No relevant nonfinancial relationship exists. |
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AAA DISCLOSURE: Financial - No relevant financial relationship exists. |