Molecular Analysis of Thymopentin Binding to HLA-DR Molecules

Abstract

Thymopentin (TP5) triggers an immune response by contacting with T cells; however the molecular basis of how TP5 achieves this process remains incompletely understood. According to the main idea of immunomodulation, we suppose that it would be necessary for TP5 to form complex with human class II major histocompatibility complex DR molecules (HLA-DR) before TP5 interacts with T cells. The uptake of TP5 by EBV-transformed B cells expressing HLA-DR molecules and the histogram of fluorescence intensities were observed by using fluorescent- labeled TP5, testifying the direct binding of TP5 to HLA-DR. The binding specificity was confirmed by the inhibition with unlabeled TP5, suggesting the recognition of TP5 by HLA-DR. To confirm the interaction between TP5 and HLA-DR, the complex formation was predicted by using various modeling strategies including six groups of trials with different parameters, alanine substitutions of TP5, and the mutants of HLA-DR. The results demonstrated that TP5 and its alanine substitutions assumed distinct conformations when they bound to HLA-DR. The observation further showed that there was flexibility in how the peptide bound within the binding cleft. Also, the molecular analysis supplemented a newly important discovery to the effect of Val anchor on TP5 binding HLA-DR, and revealed the important effects of Glu11 and Asn62 on the recognition of TP5. These results demonstrated the capability of TP5 to associate with HLA-DR in living antigen presenting cells (APC), thereby providing a new and promising strategy to understand the immunomodulation mechanism induced by TP5 and to design potential immunoregulatory polypeptides.

Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs

“…The molecular formula is C 30 H 49 N 9 O 9 , and the molecular weight is 679.77. TP‐5 is a valuable component of thymopoietin II in thymic secretions 14‐18 . Thymopoietin II is a single polypeptide isolated from thymic hormone and is composed of 49 amino acids; however, the peptide chain composed of 5 amino acids displays the same physiologic function as thymopoietin II, and thus, this pentapeptide is called thymopentin 14‐18 .…”

“…Some studies have shown that TP‐5 exerts a significant immunomodulatory effect. For example, it can increase the levels of cAMP, promote T‐cell differentiation, and bind to T‐cell‐specific receptors to elevate the levels of intracellular GMP—thus inducing a series of intracellular reactions and playing a role in regulating the immune function of the body 14‐18 . TP‐5 can additionally induce T‐cell differentiation, promote the development, maturation and activation of T lymphocyte subsets and restore the proportion of CD4/CD8 to normal 14‐18 .…”

Affinity and Specificity of Levamlodipine-Human Serum Albumin Interactions: Insights into Its Carrier Function

“…This is not always practical. For a specific ligand binding with different receptors, we are probing interactions between the ligand and different receptors through the change of sequences of the receptors (1,3,4). During the process of a specific ligand binding with a specific receptor, different intermediate binding modes (states) have different structures and binding energies with different set of contact interactions between the ligand and the receptor (Fig.…”

Atopic Dermatitis: Drug Delivery (Management) and Approaches (Strategies) in Perspective

“…Thymopentin (31)(32)(33)(34)(35)(36)(37)(38) Thymopentin (31) an immuno-stimulant (32), is a thymic polypeptide (33), which interacts with T cells (34,35), causing T -helper cell activation resulting in enhanced interleukin-2 production with subsequent proliferation of cytotoxic T lymphocytes and natural killer cells which are capable of producing immune interferon (36), thus helps to improve immunological condition(s) including atopic dermatitis (37).…”