Association of HLA-DRB1 Alleles with Rheumatic Fever and Rheumatic Heart Disease: A Meta-analysis

Poomarimuthu, Maheshkumar; Thirunavukkarasu, Ramasamy; Govindan, Ramajayam; Rathinavel, Andiappan; Nagarajan, Ganesh; Kadiam, Sony; Jayalakshmi, Mariakuttikan

doi:10.1080/08820139.2020.1822864

Cited by 2 publications

(1 citation statement)

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“…Certain MHC alleles provide so-called "protection" toward the development of immune-related diseases due to peculiarities of antigen presentation, which affect the engagement of T cells [143,144]. "Protective" allele means that the risk of AD initiation in individuals carrying this allele is statistically lower than that for healthy donors, representing the average population [145][146][147][148]. Interestingly, the protein products of MHC-II protective alleles often differ from the products of risk alleles only by several amino acid residues localized in the TCR contact sites or near the key positions of the peptide-binding groove [149].…”

Section: The Role Of Protective Mhc-ii Alleles In the Development Of ...mentioning

confidence: 99%

MHC Class II Presentation in Autoimmunity

Ishina

Захарова

Kurbatskaia

et al. 2023

Cells

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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.

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