Immunity
ArticleDisruption of T lymphocyte positive and negative selection in mice lacking the CD8 β chain
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High-affinity CD8 variants enhance the sensitivity of pMHCI antigen recognition via low-affinity TCRs
2023, Journal of Biological ChemistryTL and CD8αα: Enigmatic partners in mucosal immunity
2010, Immunology LettersCitation Excerpt :Although CD8αβ appears to be a bona fide co-receptor, there is ample evidence to suggest a different role for CD8αα in T cell activation [61]. For example, despite the association of CD8α with p56lck and LAT, CD8α homodimers cannot provide the required signals for thymic selection in CD8β-deficient mice, although mature CD8 T cells in these mice are capable of mounting a cytolytic response [62–64]. It has been postulated that the intracellular domain of CD8β is responsible for associating CD8αβ heterodimers with lipid rafts and, therefore, allowing a better interaction between the TCR and the signaling machinery [65,66].
Doubting the TCR Coreceptor Function of CD8αα
2008, ImmunityCitation Excerpt :The ability of the CD8α cytoplasmic tail to associate with both the early Src kinase p56lck (Veillette et al., 1988), which serves to phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) of the CD3 components, and the linker of activation of T cells (LAT) (Bosselut et al., 1999), which mediates further downstream signaling, connects CD8αα to proximal and distal TCR-CD3 activation signaling cascades. Despite this link and the capacity of CD8αα to interact with MHC class I ligands, CD8αα neither supports positive selection of MHC class I-restricted thymocytes (Crooks and Littman, 1994; Fung-Leung et al., 1994; Nakayama et al., 1994) nor does it efficiently promote the productive activation of CD8-dependent MHC class I-restricted TCRs (Renard et al., 1996; McNicol et al., 2007). Furthermore, when expressed together with CD8αβ, CD8αα may downmodulate as opposed to enhance the functional avidity of the CD8αβ-TCR:Ag-MHC activation complex (Cawthon et al., 2001; Cawthon and Alexander-Miller, 2002), meaning that the contribution of CD8αα to the TCR-CD3 activation complex can be suppressive.
Molecular cloning and characterization of carp (Cyprinus carpio L.) CD8β and CD4-like genes
2007, Fish and Shellfish ImmunologyCitation Excerpt :CD8β is shown to enhance the sensitivity of alloantigen recognition by a TCR [10] and to augment responses to a cognate peptide and related altered peptide ligands [11,12]. CD8β knockout mice have dramatically reduced numbers of peripheral CD8+ cells, indicating that CD8β is required for normal thymic differentiation and maturation of CD8 T lineage cells, with perhaps the exception of IEL (intraepithelial lymphocytes) [13–15]. Differing from CD8α, CD8β lacks the p56lck domain, and therefore it does not appear to be essential for cytotoxic effector function of CD8+ cells [14].
CD8 raft localization is induced by its assembly into CD8αβ heterodimers, not CD8αα homodimers
2007, Journal of Biological Chemistry