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библиографическое описание	краткий	полный

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РЖ ВИНИТИ 34 (BI39) 95.09-04К1.38

Polymenis, Michael.
Critical binding site amino acids of anti-Z-DNA single chain Fv molecules. Roe of heavy and light chain CDR3 and relationschip to autoantibody activity [Text] / Michael Polymenis, B.David Stollar // J. Immunol. - 1994. - Vol. 152, N 11. - P5318-5329 . - ISSN 0022-1767
Перевод заглавия: Критические аминокислоты в связывающем сайте молекул антител против Fv Z-ДНК. Роль тяжелых и легких цепей CDR3 и связь с аутоиммунной активностью
Аннотация: Bacterial expression of single chain variable fragment (scFv) domains was used to assess Ag-binding contributions of specific regions and residues in a mouse mAb to Z-DNA (AbZ22). A variant scFv (Z3-3) that did not bind Z-DNA had the Z22 light chain but differed from the Z22 heavy chain at four complimentarity determining region 3 (CDR3), one FR4 and five V[H] segment residues. Gene segment swapping and site-directed mutagenesis indicated that the major contribution of the Z22 heavy chain is its CDR3. A scFv with the CDR3H-FR4H of Ab Z22 and the V[H] segment of Z3-3 had the same selective high affinity Z-DNA binding as Z22. Some Z-DNA binding was retained even when the CDR3H-FR4H of Ab Z22 was combined with a V[H] segment that shared only 44% sequence identity with Z22. Directed mutations indicated further that residues N99 and 598 in heavy chain CDR3 and F96 in light chain CDR3 were particularly important for Ag binding. Certain substitutions in CDR3H converted the highly selective Z22 Fv into a polyreactive Fv with autoantibody-like binding to B-DNA and denatured DNA. In a graphic molecular model, heavy chain N99 protrudes from the CDR3 loop at the base of the Ag-binding groove, and the light chain F96 is barely exposed on the base of this groove; the light chain F96 may be important in heavy chain-light chain association. Autoantibody and immunization-induced Ab to nucleic acid can be built on a very similar framework and differ by a small number of amino acid CDR3H residues. США, Dep. Biochem., Tufts Univ. Med. Sch., Boston, MA 02111. Библ. 62

ГРНТИ	34.43.33

ВИНИТИ 341.43.33.05
Рубрики: АНТИТЕЛА
ПРОТИВ ДНК
СВЯЗЫВАЮЩИЕ САЙТЫ
ЛИМФОЦИТЫ Т
РЕЦЕПТОР CDR3
АУТОИММУННАЯ АКТИВНОСТЬ
МЫШИ

Доп.точки доступа:
Stollar, B.David

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