3/11/2023 0 Comments Ctla4 tcelThe authors found the soluble form of CTLA4 in sera from 14 of 64 healthy subjects. Functional studies showed that the soluble form of CTLA4 is downregulated by T-cell activation, in contrast to membrane CTLA4, which is upregulated by T-cell activation. The splicing induces deletion of the transmembrane region encoded by exon 2, resulting in the production of a soluble form of the protein with a molecular mass of 23 kD membrane CTLA4 has an apparent molecular mass of 45 kD, suggesting that the soluble form is a monomeric protein. (1999) found that nonactivated human peripheral blood T lymphocytes expressed an alternatively spliced form of CTLA4. The authors suggested that the signals in organ tissues may reflect passenger lymphocytes. Northern blot analysis detected multiple human transcripts of 1, 2.4, 5, and 7 kb at high levels in spleen, thymus, and peripheral blood leukocytes lesser expression of the 2.4- and 5-kb transcripts was detected in multiple tissues, including testis, uterus, colon, heart, and brain. There are also similarities in noncoding regions, suggesting conserved transcriptional control. The deduced 223-amino acid human protein shows high homology to the mouse protein. (1999) reported the complete revised sequence of the human and mouse CTLA4 genes. Each monomeric polypeptide contains a high affinity binding site for the costimulatory molecules B7-1 and B7-2. (1995) demonstrated that the CTLA4 protein is a homodimer interconnected by a disulfide bond in the extracellular domain at cysteine residue 120. Northern blot analysis detected 2 CTLA4 mRNA transcripts of 1.8 and 0.8 kb in activated peripheral blood T cells. The cytoplasmic tail contains 2 potential phosphorylation sites. The putative protein contains a leader sequence, a V domain, a transmembrane domain, and a cytoplasmic tail encoded by 4 exons, respectively. (1991) isolated several cDNA clones corresponding to the human CTLA4 gene from a stimulated peripheral blood cell human cDNA library. The predicted protein shares 76% overall homology and complete identity in the cytoplasmic domain with the mouse protein. (1988) used a mouse Ctla4 probe to isolate a partial sequence for the human CTLA4 gene from a genomic cDNA library. Laurence is amfAR’s senior scientific consultant.Dariavach et al. Nicolas Chomont and Remi Fromentin of the University of Montreal.ĭr. Cameron of the University of Melbourne Drs. The authors conclude that “combined targeting of these pathways may be superior in terms of reversing latency and eliminating latently infected cells.”ĪmfAR was a funder of this research Authors of this paper include amfAR grantees Dr. The researchers went on to identify specific genes linked to PD1 and CTLA4 that appeared responsible for maintaining that latent state. Those cells in blood and tissue containing two immune proteins, PD1 and CTLA4, proved to contain more latent virus than their counterparts lacking those proteins. The authors collected large amounts of CD4+ T cells from 21 people with HIV on antiretroviral therapy (ART) and obtained lymph node biopsies from eight of them. More characterization of latently infected cells was needed. This active state is typically necessary for the cells to become targets for elimination. It was known that certain proteins that inhibit the ability to activate a T cell, the “immune checkpoint proteins,” concurrently block the ability to convert that cell from a latent to an active state of HIV growth. A collaborative research effort sought to define how to identify such cells in a first step toward reversing latency and eliminating HIV reservoirs. But some subtypes of those reservoir cells that could be targeted in a cure strategy may represent much greater obstacles than others because they are both enriched for latent HIV and better able to resist reactivation. HIV reservoirs, whose persistence is the primary impediment to a cure for HIV, predominantly involve CD4 memory T cells. Professor Sharon Lewin (Photo: The Doherty Institute)
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |