T cell receptor-HLA Interaction
Project leaders: Sami Djoulah & Emmanuel Mignot
The T cell receptor is the natural receptor of the HLA-peptide complex and interacts directly with MHC molecules, notably their CDR regions. The goal of this project will be to combine analysis of TCR and HLA in the context of disease, vaccination/immune alterations and populations. We would expect samples to be CD4 or CD8 T cells and to have full HLA class I and class II typing by NGS.
Required NGS HLA loci: HLA-A, B, C, DRB1, DRB3/4/5, DQB, HLA-DQA, DPA, DPB
Optional NGS HLA Loci: MICA, MICB
Subprojects for this component will include:
Disease study: This will involve a meta-analysis of all autoimmune disorders for the report of the workshop and individual disease analysis that will be lead by specific investigators. These may include case/control and longitudinal studies.
TCR usage/HLA study: This will involve studying changes in usage and CDR1/CDR2 regions as a function of HLA types. The analysis will be performed in control samples, and could possibly be applied to specific diseases.
Technical and nomenclature study: This will involve comparisons of various commercially available techniques using the same samples and normalization of nomenclature. We plan to have five samples that will be part of quality control to be sequenced by all labs doing NGS. Finally, pipelines for TCR analysis will be made available to all other components.
Transplantation study: This will involve the study of the TCR repertoire in relation to HLA in transplantation.
GWAS-TCR study: We will ask GWAS data or extra 1ug DNA to be contributed when available to study genome wide and TCR cis QTL effects on the TCR repertoire. This will allow HLA imputation studies.
Analysis and publications:
Raw sequences for TCR and HLA NGS will be hosted by the workshop so that multiple analytical techniques can be performed. Data analysis will be conducted separately for each study. It will be possible to publish separately these sub-studies providing the component heads agree and verify there is no conflict.