Specific Inhibition of T cell by Fab to Peptide/MHC Complex
| المؤلف الرئيسي: | Al Jabri, Abid Abd Allah M. (Author) |
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| التاريخ الميلادي: |
2010
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| موقع: | ملبورن |
| الصفحات: | 1 - 44 |
| رقم MD: | 752466 |
| نوع المحتوى: | رسائل جامعية |
| اللغة: | الإنجليزية |
| الدرجة العلمية: | رسالة ماجستير |
| الجامعة: | RMIT University |
| الكلية: | School of Medical Science |
| الدولة: | أستراليا |
| قواعد المعلومات: | +Dissertations |
| مواضيع: | |
| رابط المحتوى: |
الناشر لهذه المادة لم يسمح بإتاحتها. |
| المستخلص: |
The activation of T helper cells against graft tissue is a cause of antibody mediated rejection. Specifically, blocking the interaction between antigen presenting cells (APC) and T cell receptors (TCR) by antigen-binding fragment (Fab) would avoid further T cell differentiation. Determining all immunogenic epitopes on the mismatched HLA is the first step in the production of Fab. Immunogenic epitopes are those foreign, superficial peptides that have a high binding affinity to MHC II on APCs. A mismatched HLA sequence can be compared with all HLA alleles of the recipient to exclude any similar sequence being immunogenic. Furthermore, the location of peptides can be identified by examining the three dimensional picture of HLA molecules. Moreover, each major histocompatibility complex (MHC) groove has a specific binding affinity to every peptide generated as a result of HLA digestion, and those peptides with a low binding affinity would have a reduced possibility of being presented to TCR. The binding affinity of each peptide to MHC II can be predicted online in the Immune Epitope Database (IEDB). Combining these three procedures illustrated thirteen immunodominate epitopes, which is quite high number. These peptides can be complexed with MHC II in bacteria. The artificial complex is then presented to the phage display in order to select a Fab that can bind to this complex. However, the hypothesis presented in this study requires further investigation and experiments to assess the efficiency of Fab production, blocking, and its stability in vitro and in animal models. |
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