Tcellsreceptorer

Tcellsreceptorer, in immunology usually called the T-cell receptor (TCR), is a membrane-anchored protein on T lymphocytes that recognizes peptide antigens bound to major histocompatibility complex (MHC) molecules on antigen-presenting cells. Most TCRs are αβ, comprising α and β chains; a minority are γδ TCRs composed of γ and δ chains. αβ TCRs primarily mediate adaptive immune responses and recognize peptide-MHC complexes, whereas γδ TCRs often respond to non-peptide antigens and can function in more innate-like ways in tissues.

TCR diversity arises from somatic recombination of V(D)J gene segments during T cell development in the thymus, orchestrated by RAG1/2. Alpha and gamma chains rearrange V and J segments; beta and delta use V-D-J. Junctional diversity is increased by random nucleotide insertions by terminal deoxynucleotidyl transferase (TdT) and N region additions. The resulting TCR variable region, especially the CDR3 loop, determines antigen specificity.

Recognition and signaling occur when the TCR engages peptide antigens presented by MHC class I or II. CD4 or CD8 co-receptors aid in stabilizing this interaction. The TCR associates with the CD3 signaling complex and zeta chains, transmitting activation signals that trigger T cell responses.

Development and selection in the thymus shape the repertoire. Positive selection favors T cells that recognize self-MHC, while negative selection eliminates highly self-reactive clones, contributing to central tolerance; peripheral tolerance further regulates activity.

Clinical relevance includes TCR-based therapies, such as TCR-engineered T cells (TCR-T) for cancer, which differ from CAR-T approaches by recognizing peptide-MHC complexes. TCR repertoire analysis informs disease diagnostics, vaccine design, and immunotherapy, though challenges include MHC restriction and potential cross-reactivity.