fa استفاده از ایمونولوژی محاسبه ای برای تعیین شکاف های سطحی ناحیه متصل شونده به آنتی ژن در مولکول ایمونوگلوبولین Gانسان تخصصي Special پژوهشي Research <span style="font-size:9pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">زمینه و هدف:</span></span></b> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">&nbsp;ایمونوگلوبولین</span></span><b> </b><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">ها</span></span>] <span dir="LTR" style="color:black">i</span>mmunoglobulins (Igs) [<span style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> گلیکوپروتئینهای دفاعی بدن هستند که </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">میکروبها را به صورت اختصاصی شناسایی و تخریب می‌کنند. </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">ناحیه ای از </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">آنتی بادی که به آنتی ژن</span></span></span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">متصل میشود، </span></span></span>fragment of antigen binding (Fab) <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">نامیده میشود که حاوی </span></span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">دومینهای</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">متغیر و یک دومین</span></span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">ثابت از زنجیره های ســبک و ســنگین میباشد</span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">. </span></span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">ایدیوتیپها که اپیتوپهای واقع بر ناحیه متغیر ایمونوگلوبولینها هستند</span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">، برای ردیابی و هدفگیری سلولهای </span></span>B<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> سرطانی بکار میروند و</span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> معمولا نزدیک شکاف های سطحی </span></span>Ig<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">ها واقع شده اند. هدف این پژوهش </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">بــکارگیری ایمونولــوژی محاسبه ای بـرای تعیـین شکاف های سطحی </span></span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">ناحیه</span></span>&nbsp; Fab <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">می باشد.</span></span></span></span></span></span><br> <span style="font-size:9pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">مواد و روشها:</span></span></b><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> توالی و ساختار سوم مولکول ایمونوگلوبولین</span></span>G <b>(</b>IgG)<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> مرجع انسان در پایگاه داده </span></span>PDB<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> (</span></span>Protein Data Bank<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">) بدست آمدند. </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">شکاف های سطحی ناحیه </span></span>Fab<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">-</span></span>IgG <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">توسط نرم افزارهای</span></span> Profunc <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">در پایگاه اینترنتی </span></span><a href="http://www.ebi.ac.uk/thornton-srv/databases/profunc"><span dir="LTR" style="text-decoration:none"><span style="text-underline:none">http://www.ebi.ac.uk/thornton-srv/databases/profunc</span></span></a><span style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> &nbsp;و </span></span>Isocleft finder<span style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> تعیین گردیدند.&nbsp; </span></span><span lang="FA" style="font-size:10.0pt"><span style="font-family:"B Lotus""></span></span></span></span></span></span><br> <span style="font-size:9pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b>&nbsp;</b><b><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">یافته ها</span></span></b><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">:</span></span>&nbsp; <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">ده شکاف در سطح مولکول </span></span>IgG<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> توسط نرم افزار </span></span>Cleft Analysis<span style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> شناسایی شدند. دو تا از <span style="color:black">بزرگترین این</span></span></span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">شکاف ها</span></span></span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">در</span></span></span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">ناحیه</span></span></span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">متغیر </span></span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">و سومین </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">شکاف در ناحیه</span></span></span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">ثابت </span></span></span><span dir="LTR" style="color:black">Fab</span> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">&nbsp;واقع شده اند.</span></span></span> &nbsp;<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">همچنین سه&nbsp; </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">شکاف توسط نرم افزار </span></span>Isocleft finder <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">شناسایی شدند که دو تا از <span style="color:black">آنها از اشتراک دومینهای متغیر و ثابت </span></span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">و سومی </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black">از دومینهای ثابت </span></span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">ناحیه</span></span> <span dir="LTR" style="color:black">Fab </span>&nbsp;<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">تشکیل</span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"><span style="color:black"> شده اند.</span></span></span> &nbsp;<span lang="FA" style="font-size:10.0pt"><span style="background:yellow"><span style="font-family:"B Lotus""></span></span></span></span></span></span></span><br> <span style="font-size:9pt"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">نتیجه گیری:</span></span></b> <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">شکاف های سطحی </span></span>IgG <span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">شناسایی</span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> شده</span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> در این مطالعه میتوانند در تعیین اپیتوپهای مولکول </span></span>IgG<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">، ایدیوتیپهای اختصاصی و تولید آنتی بادیهای منوکلونـال اختصاصی ضد ایدیوتیپ جهت </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">رد یابی و هدف گیری سلولهای </span></span>B<span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:"> بدخیم، </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">طراحی و تولید پروتئینهای مشابه برای اهداف تشخیصی و درمانی </span></span><span lang="FA" style="font-size:10.0pt"><span b="" lotus="" style="font-family:">مورد استفاده قرار گیرند.</span></span></span></span></span></span><br> &nbsp; <span style="font-size:10pt"><span style="line-height:12pt"><span new="" roman="" style="font-family:" times=""><b>Background</b>: Immunoglobulins (Igs) are protective glycoproteins specifically identify and eradicate microbes. Fragment of antigen binding (Fab) is a portion of antibody which binds to antigen and consists of one variable and one constant domain of one heavy and one light chain. Idiotypes, epitopes situated on Igs variable region, could be exploited to monitor and target malignant B cells and are usually located near the surface clefts of the Igs. In present study the superficial clefts in human IgG Fab region have been determined by computational data analysis.&nbsp;</span></span></span><br> <span style="font-size:10pt"><span style="line-height:12pt"><span new="" roman="" style="font-family:" times=""><b>Methods</b>: Amino acid sequences and third structure of reference human IgG were found in Protein Data Bank (PDB). Surface clefts in IgG-Fab have been defined by Profunc software in <span style="color:black"><a href="http://www.ebi.ac.uk/thornton-srv/databases/profunc"><span style="color:black"><span style="text-decoration:none"><span style="text-underline:none">http://www.ebi.ac.uk/thornton-srv/databases/profunc</span></span></span></a> data bank and Isocleft finder software on reference human IgG sequence.</span></span></span></span><br> <span style="font-size:10pt"><span style="line-height:12pt"><span new="" roman="" style="font-family:" times=""><b><span style="color:black">Results</span></b><span style="color:black">: Ten clefts on human IgG</span> <span style="color:black">were recognized by Cleft analysis software. Two of the biggest clefts were located to variable region and third one was sited in constant region of the Fab. Also three clefts on human IgG</span> <span style="color:black">were identified by Isocleft finder software in Fab region. First two clefts were in variable and constant domains and third one was in constant domains of the Fab. </span></span></span></span><br> <span style="font-size:10pt"><span style="line-height:12pt"><span new="" roman="" style="font-family:" times=""><b><span style="color:black">Conclusion</span></b><span style="color:black">: The surface clefts of human IgG identified in the present study could be useful in determination of IgG epitopes, specific idiotypes and generating specific anti- idiotypic monoclonal antibodies to monitor/ target clonally expanded malignant B cells, as well as designing and producing the similar proteins structures for diagnostic and therapeutic purposes. </span></span></span></span><br> &nbsp; IgG انسان, ایمونولوژی محاسبه ای , شکاف های سطحی Human IgG, Computational Immunology, Surface Clefts 311 324 http://aums.abzums.ac.ir/browse.php?a_code=A-10-1177-2&slc_lang=fa&sid=1 Soheila Rohani سهیلا روهانی 10031947532846009630 10031947532846009630 No Medicine, Dept. of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran. پزشک،گروه ایمونولوژی، دانشکده پزشکی، دانشگاه شاهد، تهران، ایران Fatemeh Hajighasemi فاطمه حاجی قاسمی 10031947532846009631 10031947532846009631 Yes Associate Professor, Dept. of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran. دانشیار، گروه ایمونولوژی، دانشکده پزشکی، دانشگاه شاهد، تهران، ایران