Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity
Preprint
- 2 May 2018
- preprint
- Published by Cold Spring Harbor Laboratory in bioRxiv
- p. 313106
- https://doi.org/10.1101/313106
Abstract
The T cell receptor (TCR) repertoire encodes immune exposure history through the dynamic formation of immunological memory. Statistical analysis of repertoire sequencing data has the potential to decode disease associations from large cohorts with measured phenotypes. However, the repertoire perturbation induced by a given immunological challenge is conditioned on genetic background via major histocompatibility complex (MHC) polymorphism. We explore associations between MHC alleles, immune exposures, and shared TCRs in a large human cohort. Using a previously published repertoire sequencing dataset augmented with high-resolution MHC genotyping, our analysis reveals rich structure: striking imprints of common pathogens, clusters of co-occurring TCRs that may represent markers of shared immune exposures, and substantial variations in TCR-MHC association strength across MHC loci. Guided by atomic contacts in solved TCR:peptide-MHC structures, we identify sequence covariation between TCR and MHC. These insights and our analysis framework lay the groundwork for further explorations into TCR diversity.Keywords
All Related Versions
- Published version: eLife, 7.
This publication has 34 references indexed in Scilit:
- Statistical inference of the generation probability of T-cell receptors from sequence repertoiresProceedings of the National Academy of Sciences, 2012
- Structural insights into the editing of germ-line–encoded interactions between T-cell receptor and MHC class II by Vα CDR3Proceedings of the National Academy of Sciences, 2012
- Determinants of public T cell responsesCell Research, 2012
- Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selectionThe EMBO Journal, 2011
- The molecular basis for public T-cell responses?Nature Reviews Immunology, 2008
- A Highly Restricted T-Cell Receptor Dominates the CD8+T-Cell Response to Parvovirus B19 Infection in HLA-A*2402-Positive IndividualsJournal of Virology, 2006
- Statistical significance for genomewide studiesProceedings of the National Academy of Sciences, 2003
- Structure of a Complex of the Human α/β T Cell Receptor (TCR) HA1.7, Influenza Hemagglutinin Peptide, and Major Histocompatibility Complex Class II Molecule, HLA-DR4 (DRA0101 and DRB10401)The Journal of Experimental Medicine, 2002
- The Protein Data BankNucleic Acids Research, 2000
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997