A novel mutation in TAP1 gene leading to MHC class I deficiency: Report of two cases and review of the literature

Nsp1α of Porcine Reproductive and Respiratory Syndrome Virus Strain BB0907 Impairs the Function of Monocyte-Derived Dendritic Cells via the Release of Soluble CD83

“…The MHC class I complex contains several proteins, of which the most important are TAP1 and ERp57 (30). Some viruses have evolved strategies to escape immune surveillance by targeting TAP1 and ERp57 expression or function (34,41). TAP1 levels can be decreased by adenovirus E1A and the human papillomavirus, thus inhibiting peptide transport (55).…”

“…TAP also maximizes substrate diversity and affinity. Interestingly, TAP expression or function is directly affected in certain genetic diseases and is targeted by viruses and by tumor cells to disable immune surveillance (31,34). ERp57, a member of the protein disulfide isomerase family, has been widely studied for its prominent multifunctional role in the immune system at multiple cellular locations outside the ER (35) and is involved in numerous biological functions crucial to human health (36)(37)(38).…”

A human PSMB11 variant affects thymoproteasome processing and CD8+ T cell production

“…It is important to point out that this frequency of the homozygotes is overwhelmingly larger than those of extremely rare variations (reported in less than 30 patients worldwide) known to affect MHC class I-dependent generation of CD8 + T cells in humans (23)(24)(25). Those rare variations include the mutations deficient in the peptide transporter complex TAP and TAP-associated protein TAPASIN, in which patients often suffer from respiratory tract infection and skin granulomatous lesions but sometimes exhibit no clinical problems (23)(24)(25). Based on the results of this study, we would like to propose a careful and long-term analysis of health status in those rs34457782 minor allele populations, particularly in homozygotes, that carry the β5t-G49S variant, in hopes of better understanding the role of the thymoproteasome-dependent positive selection of CD8 + T cells in humans.…”

“…The frequency of the 5 homozygotes found in the 9,730 volunteers (0.051%) suggests that the β5t-G49S variation has little or no negative impact on the human populations. It is important to point out that this frequency of the homozygotes is overwhelmingly larger than those of extremely rare variations (reported in less than 30 patients worldwide) known to affect MHC class I-dependent generation of CD8 + T cells in humans (23)(24)(25). Those rare variations include the mutations deficient in the peptide transporter complex TAP and TAP-associated protein TAPASIN, in which patients often suffer from respiratory tract infection and skin granulomatous lesions but sometimes exhibit no clinical problems (23)(24)(25).…”

The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer

“…Furthermore, downregulation of beta-2 microglobulin (β 2 -m), calnexin, and transporter-associated antigen processing (TAP) subunit 1 leading to impaired HLA class I expression was found in metastatic brain lesions of BC, which was also negatively linked to the frequency of CTL infiltration [27]. The underlying molecular mechanisms responsible for deficient HLA class I expression are diverse and could be attributed to gene mutations, LOH, and tran-scriptional, posttranscriptional, and translational control, and altered oncogenic and IFN signaling [28][29][30][31][32][33]. This results in decreased tumor immunogenicity, which is consequently associated with increased malignancy, metastasis formation, worse prognosis, and poorer response to (immuno-)therapies [34][35][36][37].…”