کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9141908 | 1163886 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Biochemical and structural impact of natural polymorphism in the HLA-A3 superfamily
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کلمات کلیدی
CTLCDRβ2Mβ2-microglobulin - β2-میکروگلوبولینReverse transcriptase - ترانس کریپتاز معکوس یا وارونویسtransporter associated with antigen processing - حمل کننده همراه با پردازش آنتی ژنcircular dichroism - رنگ تابی دورانیX-ray structure - ساختار اشعه ایکسendoplasmic reticulum - شبکه آندوپلاسمی TAP - ضربه زدنcytotoxic T lymphocyte - لنفوسیت T سیتوتوکسیکComplementarity-determining region - منطقه تعریف کننده تکمیلیPosition - موقعیتVaccine - واکسنpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Class I alleles of the HLA-A3 superfamily (-A*0301, -A*1101, -A*3101, -A*3301, and -Aw*6801) share largely overlapping peptide repertoires. Cross-reactive T cell responses between HLA-A3-like molecule/peptide complexes have been demonstrated in vitro and during natural diseases. In spite of this immune relatedness, HLA-A3-like molecules exhibit noticeable differences in their antigen-selecting and -presenting properties. Identifying molecular and structural features responsible for these differences is important for understanding how natural polymorphism leads to functional divergence within the HLA-A3 superfamily. Towards this goal, we used an approach that combines thermal stability data on recombinant, soluble HLA-A3-like molecules complexed with a nonamer and decamer HIV-1 peptide, together with a detailed structural analysis of these HLA-A3-like molecule/peptide complexes based on crystal and molecular model structures. Our studies revealed the importance of residues 9 and 67 for modulating peptide selection within the B pocket; of residue 97 for modulating peptide selection within the F pocket interdependently with the presence (or absence) of a middle, secondary anchor residue; and of residues 70, 73, 97, 152, and 156 for modulating peptide presentation in the central region of the groove that leads to altered antigenic surfaces. Overall, our detailed assessment of the biochemical and structural impact of natural polymorphism within the HLA-A3 superfamily has permitted to understand how HLA-A3-like molecules differ at the level of their primary and secondary anchor pockets causing fine differences in their peptide-selecting and -presenting properties. A better understanding of the molecular immunological properties of HLA-A3-like molecules is significantly important for the rationale design of broad peptide-based vaccines.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 42, Issue 11, July 2005, Pages 1331-1344
Journal: Molecular Immunology - Volume 42, Issue 11, July 2005, Pages 1331-1344
نویسندگان
Lenong Li, Marlene Bouvier,