Structurally, the binding surface of both classes of MHC proteins is comprised of two domains this surface originates from a single α-chain for MHC class I and from an α-chain and β-chain heterodimer for MHC class II ( 12). Antigen-processing pathways differ between both MHC classes however, all pathways lead to the expression of a fully assembled peptide-MHC (pMHC) complex at the cell surface for TCR recognition ( 13). These MHC molecules present processed peptides at the cell's surface for recognition by T cells through their specific TCRs ( Fig. Antigen presentation by both classes of MHC proteins is an essential process in adaptive immunity ( 11, 12).
#Tcr repertoire imgt professional#
MHC class I proteins are expressed by all nucleated cells and are recognized by cytotoxic CD8 + T cells while MHC class II proteins are expressed by professional antigen-presenting cells (APC) such as dendritic cells, macrophages, and B cells for recognition by CD4 + T cells. TCRs are of no consequence in the absence of their critical interaction partners, MHC molecules. Importantly, immature T cells commit to either an αβ or γδ lineage during V(D)J recombination, where the commitment to αβ is facilitated by the successful recombination of the β-chain and commitment to γδ is facilitated by successful recombination of both the γ and δ chain ( 9). Both combinational and junctional diversity grant T cells a substantial range of antigen specificities, potentially accounting for 10 15 to 10 20 possible TCR chains ( 8). The overall combinatorial diversity of the gene segments is accompanied by junctional diversity, which is driven by the random addition or deletion of nucleotides at junctions between gene segments. TCRα and γ chains are comprised of V and J gene segments, while TCRβ and δ chains also include the D gene segment, offering more diversity in structure. The variable region is assembled from variable (V), diversity (D), and joining (J) gene segments through an ordered process called V(D)J recombination, in which one allele of each gene segment is randomly recombined with other gene segment alleles to form a functional antigen recognition region ( Fig. Regardless of type, the chains of a TCR contain an N-terminus variable region capable of antigen recognition and a C-terminus constant region. Naïve T cells become antigen-experienced T cells after encountering their cognate antigen presented on major histocompatibility complex (MHC) molecules through their TCRs. CD4 + T cells execute helper functions while CD8 + T cells are cytotoxic ( 4).
The thymus is also where T cells differentiate from an initial CD4/CD8 double-positive state into either a CD4 + or CD8 + lineage. Immature T cells migrate from hemopoietic tissues to the thymus where they mature into naïve T cells that express a unique and functional T-cell receptor (TCR) that grants them the ability to recognize specific antigens ( 3). Functionally, T cells kill infected cells or release cytokines to recruit other immune cells after recognizing foreign antigens presented on infected cells ( 2). T cells are critical mediators of adaptive immunity, specifically driving cellular immunity as opposed to B cells that govern humoral immunity. Our immune system is composed of the innate and adaptive immune systems the innate immune system protects against general threats and conserved pathogenic sequences while the adaptive immune system targets and retains memory of specific pathogens ( 1).
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