T Cell Receptor Profiling and Adaptive Immune Responses

T cells lie at the heart of adaptive immunity by deploying T cell receptors (TCRs) to detect peptide antigens presented by major histocompatibility complex (MHC) molecules. Diversity in TCR repertoires is generated through V(D)J recombination, producing millions of distinct clonotypes capable of recognising a vast array of pathogens and altered self-antigens. Advances in high-throughput sequencing and single-cell technologies now enable detailed mapping of TCR sequences alongside transcriptional phenotypes, illuminating clonal expansion, differentiation trajectories and functional states. Profiling these repertoires has deepened understanding of host defence, autoimmunity and immunosenescence, while informing vaccine design, checkpoint immunotherapy and strategies to monitor transplant rejection. Contemporary efforts integrate computational pipelines with machine-learning approaches to decode antigen specificity and to trace lymphocyte lineage commitment across developmental and disease contexts.

Research from Nature Portfolio

Recent studies have explored fundamental drivers of TCR diversity, developed innovative single-cell analysis pipelines and charted age-related shifts in CD8+ T cell clones. One investigation into the evolutionary basis of TCRα diversity revealed that species-specific sequence microhomologies direct the outcomes of V(D)J recombination, shaping repertoire breadth across vertebrates. A novel computational framework called Dandelion extends single-cell RNA and immune receptor sequencing by improving V(D)J contig annotation, distinguishing productive from non-productive rearrangements and enabling pseudotime inference of thymic and peripheral lymphocyte lineages. In parallel, lifespan analyses of influenza-specific CD8+ T cells demonstrated that the molecular signatures of newborn and child-derived clones reappear in older adults, indicating a clonal reset that influences antiviral potency and functional avidity in ageing immunity.

T Cell Receptor Profiling and Adaptive Immune Responses publication trend

The graph below shows the total number of articles in t cell receptor profiling and adaptive immune responses across all publications each year (not limited to Nature Index journals).

Technical terms

T cell receptor (TCR): A heterodimeric surface protein on T lymphocytes that recognises peptide–MHC complexes and initiates antigen-specific responses.

V(D)J recombination: A somatic gene rearrangement process that assembles variable (V), diversity (D) and joining (J) gene segments to generate diverse TCR and antibody repertoires.

scVDJ-seq: Single-cell sequencing methodology that captures paired immune receptor sequences alongside cellular transcriptomes.

Clonal expansion: The proliferation of antigen-specific T cells following activation, leading to observable increases in particular TCR sequences.

Antigen specificity: The unique recognition capacity of a given TCR for a particular peptide–MHC complex.

References

1. Origin and evolutionary malleability of T cell receptor α diversity. Nature (2023).
2. Dandelion uses the single-cell adaptive immune receptor repertoire to explore lymphocyte developmental origins. Nature Biotechnology (2023).
3. Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan. Nature Immunology (2023).
4. Identification of SARS-CoV-2-specific T cell and its receptor. Journal of Hematology & Oncology (2024).
5. VDJdb: a curated database of T-cell receptor sequences with known antigen specificity. Nucleic Acids Research (2017).
6. Overview of methodologies for T-cell receptor repertoire analysis. BMC Biotechnology (2017).