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Monash University
Monash UniversityRheumatoid arthritis (RA) is an autoimmune immune disease, characterized by joint swelling, pain, stiffness, thereby limiting the patient's ability to act.
Rheumatoid arthritis (RA) is an autoimmune immune disease, characterized by joint swelling, pain, stiffness, thereby limiting the patient's ability to act.
The HLA locus is the most dynamic region in the human genome, which makes HLA molecules present a wide range of peptides.
The destruction of T cell tolerance can be attributed to a variety of mechanisms, including abnormal T cell receptor ( TCR ) -HLA docking topology, changes in peptides bound to HLA molecules, molecular simulations, and the generation of new epitopes.
It is well known that human leukocyte antigen (HLA)-DR4 can increase the susceptibility of RA.
In this study, the research team used transgenic mice to express human HLA-DR4 molecules and studied how T cells recognize these HLA-DR4 molecules at the molecular and cellular levels.
Studies have found that in HLA-DR4 transgenic mice, due to selective clonal expansion from pre-immunization procedures, immunization with Fibβ-74cit 69-81peptide can result in HLA-DR4 dicitrulline epitope (Fibβ-74cit 69-81).
In HLA-DR4 transgenic mice, due to selective clonal expansion from pre-immunization procedures, immunization with Fibβ-74cit 69-81peptide can lead to the tetramerization of HLA-DR4 dicitrulline epitope (Fibβ-74cit 69-81 ) The body exhibits a biased T cell receptor (TCR ) β chain usage of T cells.
Highly similar T cell receptors, which may have similar recognition characteristics, are also present in "RA susceptible" people expressing HLA molecules .
Influence of TCR point mutation on PMHC Ⅱ interface
PMHC has Ⅱ interface TCR point mutation of PMHC has Ⅱ interface TCR Effect of point mutationsThe study revealed that the development of rheumatoid arthritis may have an immune marker by studying how T cells recognize the altered joint proteins in the complex formed with "susceptibility" HLA molecules .
This study may have an immune marker for the development of rheumatoid arthritis.
sciencemag.
sciencemag.
org/content/6/58/eabe0896">More information:.
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JJ Lim el al, "The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR," Science Immunology (2021) immunology.
sciencemag.
org/look .
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6 / sciimmunol.
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