Disease relevance of Havcr1

• TIM-1 is genetically linked to asthma and is a receptor for hepatitis A virus, but the endogenous ligand of TIM-1 is not known [1].
• In vivo, the use of antibody to TIM-1 plus antigen substantially increased production of both interleukin 4 and interferon-gamma in unpolarized T cells, prevented the development of respiratory tolerance, and increased pulmonary inflammation [2].
• T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3) and TIM-1 molecules are differentially expressed on human Th1 and Th2 cells and in cerebrospinal fluid-derived mononuclear cells in multiple sclerosis [3].
• These results are the first to suggest that TIM-1 antibody may serve as a potent adjuvant in the development of new influenza virus vaccines [4].
• We investigated the ability of Abs blocking Tim-1 or Tim-3 ligand-binding activity to prevent and treat murine experimental allergic conjunctivitis (EC), a Th2-mediated disease [5].

Psychiatry related information on Havcr1

• Uncovered: the family relationship of a T-cell-membrane protein and bacterial toxins [6].

High impact information on Havcr1

• Three of the family members (Tim-1, Tim-3, and Tim-4) are conserved between mouse and man [7].
• Genomic association of the TIM family and polymorphisms in both Tim-1 and Tim-3 in different immune-mediated diseases suggest that the family may have an important role in regulating immunity, both in terms of normal immune responses and in diseases like autoimmunity and asthma [7].
• This increased avidity for peptide-MHC depends on TCR reorganization and is sensitive to the cholesterol content of the T cell membrane [8].
• TIM-1 induces T cell activation and inhibits the development of peripheral tolerance [2].
• Here we show that TIM-4, which is expressed by antigen-presenting cells, is the ligand for TIM-1 [1].

Biological context of Havcr1

• These results suggest that a direct interaction between anti-TNF and T cell membrane-anchored TNF could account for the observed modulation of cytokine gene expression [9].
• Expression cloning and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the HAV cellular receptor 1 (HAVcr-1) [10].
• Regulation of tyrosine phosphorylation in isolated T cell membrane by inhibition of protein tyrosine phosphatases [11].
• Co-operation has two components: enhancement of the affinity of MHC/peptide-TCR interaction, and signal transduction through the T cell membrane [12].
• However, T-cell membrane fluidity decreases with age, whereas B-cell membrane fluidity does not change; in old mice, T-cell membranes are significantly less fluid than old B-cell membranes [13].

Anatomical context of Havcr1

• Light microscopy and electron microscopy revealed a close association between the T cell membrane and the cell wall of N. asteroides, with possible damage to the latter structure [14].
• Moreover, higher TIM-1 expression was associated with clinical remissions and low expression of IFN-gamma mRNA in cerebrospinal fluid mononuclear cells [3].
• Expression of T cell immunoglobulin- and mucin-domain-containing molecules-1 and -3 (TIM-1 and -3) in the rat nervous and immune systems [15].
• These studies suggest that TIM-1 can regulate macrophage activation and alter the co-stimulatory properties of macrophages and thus may contribute to allergic inflammatory diseases such as asthma [16].
• We postulate that an antigen-Ia complex may provide for close physical interactions between effector and target cells and may approximate putative T cell membrane-bound activating molecules (as yet unidentified) with the macrophage plasma membrane [17].

Associations of Havcr1 with chemical compounds

• Finally, we provide evidence that TIM-1 can be phosphorylated on tyrosine and that TIM-1 costimulation requires its cytoplasmic tail and the conserved tyrosine within that domain [18].
• These results constitute evidence that TIM-1 directly couples to phosphotyrosine-dependent intracellular signaling pathways [18].
• Transfer of the ADP-ribose moiety from NAD onto extracellular arginine residues on T-cell membrane proteins is mediated by glycosylphosphatidylinositol-linked cell surface ARTs [19].
• These results suggest that cyclosporin A mediates its effect on cells through more than one cyclophilin and that cyclosporin A-induced misfolding of T-cell membrane proteins normally mediated by CPH2 plays a role in immunosuppression [20].
• Because L-lactate may be transported bidirectionally through the T cell membrane in vivo, different physiologic roles of L-lactate transport are discussed [21].

Regulatory relationships of Havcr1

• Con A stimulation of T-cell membrane transplanted BW 5147 showed that it is possible to induce a mitogen dose-dependent T-cell growth factor production [22].

Other interactions of Havcr1

• Ectopic expression of TIM-1 during T cell differentiation results in a significant increase in the number of cells producing IL-4 but not IFN-gamma [18].
• Furthermore, TIM-1 expression provides a costimulatory signal that increases transcription from the IL-4 promoter and from isolated nuclear factor of activated T cells/activating protein-1 (NFAT/AP-1) elements [18].
• Mouse T cell membrane proteins Rt6-1 and Rt6-2 are arginine/protein mono(ADPribosyl)transferases and share secondary structure motifs with ADP-ribosylating bacterial toxins [23].
• The data suggest that other T cell membrane molecules contribute to activation of Mphi effector function by stimulation of M phi TNF-alpha production [24].
• CTLA-4 is a predicted T cell membrane receptor homologous to CD28, which also binds the B7 counter receptor, but whose distribution and function are unknown [25].

Analytical, diagnostic and therapeutic context of Havcr1

• In vitro stimulation of CD4(+) T cells with a TIM-1-specific monoclonal antibody and T cell receptor ligation enhanced T cell proliferation; in T(H)2 cells, such costimulation greatly enhanced synthesis of interleukin 4 but not interferon-gamma [2].
• Our studies suggest that immunotherapies that regulate TIM-1 function may downmodulate allergic inflammatory diseases [2].
• Immunofluorescence analysis indicated that mouse Ltk- cells transfected with HAVcr-1 cDNA gained limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4 [10].
• A sensitive radioimmunoassay was constructed for detection of the T cell membrane components [26].
• No alloantibodies directed to the T cell membrane components, the putative human homologues of mouse TL antigens, were found in any of the human tissue typing sera tested [26].

References