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Application of Partial Least Square Method in Studying of the Quantitative Structure-activity Relationship of T Cell Epitopes

Author: SongZhe
Tutor: LiuWei
School: Dalian University of Technology
Course: Theoretical Physics
Keywords: Major histocompatibility complex Antigenic peptides QSAR Partial least squares
CLC: R392
Type: Master's thesis
Year: 2008
Downloads: 66
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Abstract

T cells are the most important immune cells, and its main function is mediated by cellular immunity and regulating the body's immune function. The cytotoxic T cells can be directly specific killing of tumor cells. For T cells play its immune function, need to activate the T cells of the immune response to T-cell activation, proliferation and differentiation. However T cells can not directly recognize the native antigen, it can only be identified with major histocompatibility complex MHC molecules, by the major histocompatibility complex MHC molecules presenting antigenic peptides. This paper is capable of activating cytotoxic T cells, the endogenous antigen processing presenting pathway, the antigenic peptide in combination with the major histocompatibility complex MHC class I molecules. The endogenous antigen peptide generation process: antigen-presenting cells APC internal, endogenous antigen and ubiquitin conjugating, brought by the ubiquitin proteasome. In the proteasome, endogenous antigens are processed to degrade to the antigen peptide; antigen peptide to the endoplasmic reticulum after antigenically related transporter proteins TAP transporter; in the endoplasmic reticulum, the antigen peptides with the newly generated MHC I class molecules binding antigenic peptide-MHC molecule complexes; complexes through the Golgi are transferred to the antigen-presenting cell surface, and the surface of the T cells of the T cell antigen receptor TCR binding, trimers of the TCR-antigen peptide-MHC molecules, activated T The whole process of lymphocyte immune response. Generating process by the endogenous antigen peptide shows that the composite body of the antigenic peptide-MHC class I molecules play a direct role in T cell activation. Therefore, it is important what kind of antigen peptides binding to MHC Ⅰ molecule. MHC Ⅰ class of molecules is the α chain (containing the α1, α2 and α3 three domains) and β chain (β2m) composition, wherein α1 and α2 of the antigen-binding groove constitute the class I molecule. Both ends of the binding groove is closed, so the length of the antigen peptides combined with MHC Ⅰ molecule is restricted, is generally 8 to 11. 6 constituted by the amino acid residue pockets (the Pocket the A ~~ F), in the α1 and α2 constitute the binding groove. The corresponding position of the antigen peptide binding to MHC Ⅰ molecule side chains will enter into the 6 Pocket. This structure of MHC class I molecules to determine what kind of antigen peptides to bind. Different antigen peptides and MHC class I molecule binding force is different, and in the immunological experiments by IC ₅₀ value (InhibitConcentration to achieve 50% bioeffectivity) to indicate that the size of the binding affinity. The amino acid sequence of the binding groove of MHC class I molecules is unchanged, and therefore the amino acid sequence of the antigen peptide will determine whether it can be combined with MHC Ⅰ molecule. That is, the antigenic peptide is the key to activate the T cell immune response, these antigen peptide capable of activating the T cell immune response is also called T-cell epitopes. Therefore, identification of T cell epitopes in immunology have great significance. The identification of T cell epitopes in the experimental method is to use the first synthesis of a large number of overlapping peptides, and then through the polypeptide binding experiments or T-killing effect detection selected. This experimental method is time-consuming for the low efficiency, it is necessary using theoretical methods to predict T-cell epitopes. Based on the length of the antigen peptide 9 (contains nine amino acids) model, the two-dimensional QSAR model antigen peptide, and has been the model for solving partial least squares PLS antigenic peptide with MHC class I molecules binding affinity prediction model. The model prediction accuracy rate of 66.8%. The model will help the people of MHC Ⅰ molecule binding antigen peptide processing-depth understanding of the process of presenting people have certain guiding significance for the design and development of tumor vaccines are.

Application of Partial Least Square Method in Studying of the Quantitative Structure-activity Relationship of T Cell Epitopes

Abstract

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