Which TCR chain is subject to allelic exclusion?
T-cell receptor β-chain
To ensure that T cells express a single T-cell receptor β-chain (TCR-β) — that is, allelic exclusion — TCR-β gene rearrangement is tightly regulated.
What is allelic exclusion in B cells?
Allelic exclusion is a process by which only one allele of a gene is expressed while the other allele is silenced. This phenomenon is most notable for playing a role in the development of B lymphocytes, where allelic exclusion allows for each mature B lymphocyte to express only one type of immunoglobulin.
What is allelic exclusion during B cell receptor development?
The phenomenon of monoallelic rearrangement of the antigen receptors has been coined “allelic exclusion.” During B and T cell development, at the proper developmental stage, each antigen receptor locus becomes accessible to the rearrangement machinery, and one of the two alleles undergoes rearrangement.
What is TCR beta?
The TCR is a disulfide-linked membrane-anchored heterodimeric protein normally consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules.
What is the 12 23 rule?
The 12/23 rule, which is mediated at the level of RAG-1/2 recognition and cutting4,5, specifies that V(D)J recombination occurs only between a gene segment flanked by a 12-RSS and one flanked by a 23-RSS1.
What causes allelic exclusion?
Mechanisms that have been shown to contribute to allelic exclusion include asynchronous replication of the two alleles, with rearrangement occurring at the allele that replicates early; localization of the active allele to a more central, euchromatic region of the nucleus; and DNA demethylation of the active allele.
What is the benefit of allelic exclusion?
Allelic exclusion ensures only one productively rearranged allele is expressed on the surface of each B and T cell. This is important because the adaptive immune system relies on clonal expansion of lymphocytes that are able to specifically recognize an invading pathogen.
What does TCR bind to?
TCR generally only binds peptide antigens presented on MHC. Antigen-binding affinity is lower than that of Ig for native antigen, but MHC binding by the T cell membrane co-receptors CD4 (on helper T cells) or CD8 (on cytotoxic T cells) increases the binding avidity of the T cell for the antigen-MHC complex.
Is TCR monovalent?
Using two biophysical approaches that mitigate these effects, bioluminescence resonance energy transfer and two-color coincidence detection microscopy, we show that, within the uncertainty of the methods, the membrane components of the TCR triggering apparatus, i.e. the TCR complex, MHC molecules, CD4/Lck and CD45, are …
What is the purpose of the 12 23 rule?
The 12/23 rule prevents rearrangement of V or J genes within their own clusters and ensures the obligatory inclusion of a D segment during IgH gene recombination, because the VH and JH genes are both flanked by 23RS, and the DH genes are flanked by 12RS.
What does Vdj stand for?
VDJ stands for variability, diversity, and joining, respectively, and VDJ rearrangement has 4 key characteristics that help ensure that each antigen receptor is unique.
What is isotypic exclusion?
The isotypic exclusion reflects a defined developmental sequence of light chain rearrangement, with κ preceding λ, or with a much higher probability of κ rearrangement.