Detection of antigen-specific immunity | Translational Immunogenomics Lab

Diagram that shows how B721.221 cells (~50 M) are transduced to express only one HLA allele

In our single-allele approach, B721.221 cells (~50 M) are transduced to express only one HLA allele. Immunopurified peptides are analyzed by LC-MS/MS and sequenced via an HLA-allele-specific database search (Abelin, Keskin et al Immunity 2017)

Sensitive detection of HLA-bound peptides on the tumor surface

T cell interactions with MHC presented peptides lie at the heart of any immune response. TIGL has developed and provides:

Detection of antigens, including CTAs, patient specific neoantigens, ERVs, and non-canonical peptides through optimized experimental workflows, mass spectrometry, and integrated data analysis, using clinical tissues samples
Serial HLA-peptide isolation methods enabling HLA-I and HLA-II isolation from the same sample
Mono-allelic systems to characterize the rules that govern HLA peptide processing and presentation
Proteogenomic approaches to generate patient-specific protein databases for antigen discovery

IFN-γ ELISPOT results showing CD4+ T cells specific for mutated CDK13, JPH1, and ADM2d at week 16 after vaccination and after PD-1 blockade for patient 2

Example of IFN-γ ELISPOT results are shown for CD4+ T cells specific for mutated CDK13, JPH1, and ADM2d at week 16 after vaccination and after PD-1 blockade for patient 2. Complete response kinetics to mutated peptides are also shown (Ott and Hu et al Nature 2017).

A streamlined approach for identifying and reconstructing TCRs, and testing for specificity to candidate antigens (Hu, Anandappa et al Blood 2018).

Immune-monitoring

The strength of TCR binding to cognate antigen (functional avidity) is strongly correlated with in vivo T cell effector function. TIGL has developed and provides:

ELISPOT assays and multicolor flow cytometry to investigate antigen-specific T cell responses

TCR reconstruction

TIGL has developed and provides:

A novel TCR reconstruction pipeline that enables the testing of neoantigen-specific TCRs for functional avidity as an indicator of anti-tumor activity using ELISPOT and intracellular cytokine staining

Staff

Derin B. Keskin, PhD, Immunology Lead Scientist

Katarina Pinjusic, PhD, Postdoctoral Fellow

Allison Vanasse, Research Technician

Joseph Duke-Cohan, Research Technician, Bioinformatics

Melis Akinci, Research Technician

Marwa Belhaj, Research Technician

Publications