Tapbpl, encoding the tapasin-related protein TAPBPR, is involved in the antigen processing and presentation pathway. TAPBPR acts as an MHC-I peptide editor, shaping the final peptide repertoire displayed on the cell surface, which is crucial for mounting effective antiviral and antitumoral immune responses [4,5,6]. It has also been identified as a potential immune checkpoint molecule [1,2].

In mice, administration of recombinant TAPBPL protein significantly decreased the incidence of collagen-induced arthritis (CIA), reduced clinical and pathological arthritis scores. This was related to a lower number of activated CD4 T cells, an increased number of regulatory T cells (Tregs) in the spleen, and a reduction of Th1/Th17 inflammatory cytokines in the joints and serum. TAPBPL protein also inhibited CII-specific T cell growth, Th1 and Th17 cytokine expression, and reduced the production of CII autoantibodies in the serum, suggesting its potential in treating rheumatoid arthritis (RA) [1]. In addition, in vivo administration of a soluble recombinant human TAPBPL-IgG Fc fusion protein attenuated experimental autoimmune encephalomyelitis (EAE) in mice, indicating its role in autoimmune diseases [2]. Genetic association studies have also linked TAPBPL to multiple sclerosis (MS), with higher genetically predicted levels associated with an increased risk of MS [3]. In MS, TAPBPL was found to be upregulated in B cells, CD8+ T cells, and natural killer cells compared with controls [7].

In conclusion, Tapbpl is essential for antigen presentation and immune regulation. Studies using mouse models have revealed its potential as a therapeutic target in autoimmune diseases such as RA and MS. Understanding its function provides insights into immune-mediated disease mechanisms and may lead to new treatment strategies.

References:

1. Zhang, Zhenzhen, Zhao, Jin, Lai, Kuan Chen, Lai, Laijun. 2023. Administration of Recombinant TAPBPL Protein Ameliorates Collagen-Induced Arthritis in Mice. In International journal of molecular sciences, 24, . doi:10.3390/ijms241813772. https://pubmed.ncbi.nlm.nih.gov/37762076/

2. Lin, Yujun, Cui, Cheng, Su, Min, Du, Qian, Lai, Laijun. 2021. Identification of TAPBPL as a novel negative regulator of T-cell function. In EMBO molecular medicine, 13, e13404. doi:10.15252/emmm.202013404. https://pubmed.ncbi.nlm.nih.gov/33938620/

3. Liu, Yi, Wang, Qian, Zhao, Yuhui, Chen, Jinyi, Qin, Chao. 2024. Identification of novel drug targets for multiple sclerosis by integrating plasma genetics and proteomes. In Experimental gerontology, 194, 112505. doi:10.1016/j.exger.2024.112505. https://pubmed.ncbi.nlm.nih.gov/38964432/

4. Ilca, Tudor, Boyle, Louise H. 2020. The Ins and Outs of TAPBPR. In Current opinion in immunology, 64, 146-151. doi:10.1016/j.coi.2020.06.004. https://pubmed.ncbi.nlm.nih.gov/32814254/

5. Neerincx, Andreas, Boyle, Louise H. 2017. Properties of the tapasin homologue TAPBPR. In Current opinion in immunology, 46, 97-102. doi:10.1016/j.coi.2017.04.008. https://pubmed.ncbi.nlm.nih.gov/28528220/

6. Satti, Reem, Morley, Jack L, Boyle, Louise H. 2023. Get into the groove! The influence of TAPBPR on cargo selection. In Current opinion in immunology, 83, 102346. doi:10.1016/j.coi.2023.102346. https://pubmed.ncbi.nlm.nih.gov/37295041/

7. Lin, Xin, Yang, Yuanhao, Gresle, Melissa, Taylor, Bruce V, Zhou, Yuan. . Novel plasma and brain proteins that are implicated in multiple sclerosis. In Brain : a journal of neurology, 146, 2464-2475. doi:10.1093/brain/awac420. https://pubmed.ncbi.nlm.nih.gov/36346149/