MHC Class II Presentation in Autoimmunity

Abstract

Antigen presentation by major histocompatibility complex class II (MHC-II) molecules is crucial for eliciting an efficient immune response by CD4+ T cells and maintaining self-antigen tolerance. Some MHC-II alleles are known to be positively or negatively associated with the risk of the development of different autoimmune diseases (ADs), including those characterized by the emergence of autoreactive T cells. Apparently, the MHC-II presentation of self-antigens contributes to the autoimmune T cell response, initiated through a breakdown of central tolerance to self-antigens in the thymus. The appearance of autoreactive T cell might be the result of (i) the unusual interaction between T cell receptors (TCRs) and self-antigens presented on MHC-II; (ii) the posttranslational modifications (PTMs) of self-antigens; (iii) direct loading of the self-antigen to classical MHC-II without additional nonclassical MHC assistance; (iv) the proinflammatory environment effect on MHC-II expression and antigen presentation; and (v) molecular mimicry between foreign and self-antigens. The peculiarities of the processes involved in the MHC-II-mediated presentation may have crucial importance in the elucidation of the mechanisms of triggering and developing ADs as well as for clarification on the protective effect of MHC-II alleles that are negatively associated with ADs.

Exploration of the causality of frailty index on psoriasis: A Mendelian randomization study

“…All four proteins belong to the MHC II class, which is essential for triggering an effective immune response to CD4 T cells and maintaining autoantigen tolerance. 36 However, we did not find significant differences in the expressions of these four genes in the expression profile analysis of psoriatic lesions based on GEO datasets, which needs more experiments to prove.…”

Genetically engineered CD80–pMHC-harboring extracellular vesicles for antigen-specific CD4+ T-cell engagement

“…However, it has been reported that the genetic implementation of antigenic minigenes can elicit lower reactivity compared to the exogenous loading of antigenic fragments ( Parkhurst et al, 2019 ). Exogenous loading of peptides may also require competitive displacement of the peptide already presented on MHC-II, which can be problematic when exogenous loading is required for low-affinity peptides that may still be presented and elicit T-cell responses under physiological conditions ( Stadinski et al, 2010 ; Yang et al, 2014 ; Ishina et al, 2023 ). In our system, each peptide of interest is covalently bound to the beta chain of the MHC-II molecule, allowing for the presentation of low-affinity peptides.…”

Identification of female-enriched and disease-associated microglia (FDAMic) contributes to sexual dimorphism in late-onset Alzheimer’s disease

“…Moreover, their transcriptomic signature also revealed higher expression levels of MHC class II autoantigens and Aβ binding receptor genes. It was previously reported that MHC class II autoantigen-expressing microglia were associated with various autoimmune-related neurodegenerative diseases and the development of chronic inflammatory lesions [ 116 – 119 ], which hinted at an intrinsic pathological nature of these cells. In addition to these gain-of-function genes, downregulated genes in FDAMic also suggested a loss in phagocytic activities, which may render them ineffective in clearing Aβ and other protein aggregates from the region [ 120 ] despite exhibiting Aβ binding properties.…”