{"id":95399,"date":"2018-03-11T10:15:23","date_gmt":"2018-03-11T10:15:23","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/influencia-del-polimorfismo-molecular-y-del-procesamiento-antigenico-en-al-seleccion-del-repertorio-pepta%c2%addico-de-hla-b27-implicaciones-para-la-patogenia-de-las-espondiloartropata%c2%adas\/"},"modified":"2018-03-11T10:15:23","modified_gmt":"2018-03-11T10:15:23","slug":"influencia-del-polimorfismo-molecular-y-del-procesamiento-antigenico-en-al-seleccion-del-repertorio-pepta%c2%addico-de-hla-b27-implicaciones-para-la-patogenia-de-las-espondiloartropata%c2%adas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/influencia-del-polimorfismo-molecular-y-del-procesamiento-antigenico-en-al-seleccion-del-repertorio-pepta%c2%addico-de-hla-b27-implicaciones-para-la-patogenia-de-las-espondiloartropata%c2%adas\/","title":{"rendered":"Influencia del polimorfismo molecular y del procesamiento antig\u00e9nico en al selecci\u00f3n del repertorio pept\u00eddico de hla-b27: implicaciones para la patogenia de las espondiloartropat\u00edas."},"content":{"rendered":"<h2>Tesis doctoral de <strong> Carmen Patricia Gomez Molina <\/strong><\/h2>\n<p>Hla-b27 is strongly associated with a group of rheumatic diseases collectively designed as spondyloarthropathies, that include ankylosing spondilitis (as) and reactive arthritis. An issue of the highest interest is the differential association of hla-b27 subtypes to as. The structural polymorphism influences the peptide binding specificity and other biochemical and functional features of hla-b27 determining differential association with as. Hla-b27 binds peptides with r at position 2. Hla-b27 subtypes differ among each other in their peptide specificity by differential modulation of residue preferences at the c-terminal position and at multiple secondary anchor positions. A substantial fraction of the hla-b27-bound peptide repertoire has basic residues at position 1. It is unclear whether this is determined by structural complementarity with the a pocket of the peptidebinding site, by the increased availability of peptides with dibasic n-terminal sequences resulting from their cytosolic stability, or both. hla-b*2707 is associated with as in most populations. Like the non-associated allotypes b*2706 and b*2709, it lacks d116 and shows preference for peptides with nonpolar c-terminal residues. The relationship between the peptide specificity of b*2707 and those of the diseaseassociated b*2705 and the non-associated subtypes was analysed. The b*2707-bound repertoire was as different from that of b*2705, as from those of b*2706, b*2709, or the two latter subtypes with each other. Differences between b*2707 and b*2705 were based on their c-terminal residue specificity and a subtle modulation at other positions. Differential usage of secondary anchor residues explained the disparity between the b*2707, b*2706 and b*2709-bound repertoires. T-cell crossreaction paralleled peptide sharing, suggesting that many shared ligands conserve their alloantigenic features on distinct subtypes. Our results indicate that association of hla-b27 subtypes with as does not correlate with higher peptide sharing among disease-associated subtypes or with obvious peptide motifs. to asses the role of the a pocket in the preference of hla-b27 for peptides with dibasic nterminal sequences, two b*2705 mutants were generated in which one or two a pocket surface residues stabilizing the r1 side chain were changed: e163t and e163t-w167s. The e163t mutation alone had a limited effect on binding of peptides with r1 or k1 and on the relative frequencies of nterminal residues. However, it decreased the overall stability of the molecule. The e163t-w167s mutant also bound many of the b*2705 ligands with n-terminal basic residues, but its preference for g1 was significantly decreased. The results indicate that the capacity of hla-b27 to bind peptides with n-terminal basic residues is largely independent of the canonic interactions that stabilize the r1 side chain. Thus, the prevalence of hla-b27 ligands with dibasic n-terminal sequences may be significantly influenced by the increased availability of these peptides resulting from their cytosolic stability. This confers to hla-b27 a unique capacity to present antigens generated in low amounts, but resistant to intracellular degradation.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Influencia del polimorfismo molecular y del procesamiento antig\u00e9nico en al selecci\u00f3n del repertorio pept\u00eddico de hla-b27: implicaciones para la patogenia de las espondiloartropat\u00edas.<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Influencia del polimorfismo molecular y del procesamiento antig\u00e9nico en al selecci\u00f3n del repertorio pept\u00eddico de hla-b27: implicaciones para la patogenia de las espondiloartropat\u00edas. <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Carmen Patricia Gomez Molina <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Aut\u00f3noma de Madrid<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 17\/07\/2009<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Jos\u00e9 Antonio L\u00f3pez De Castro<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: manuel Fresno escudero <\/li>\n<li>pedro Antonio Reche gallardo (vocal)<\/li>\n<li>Alberto Paradela elizalde (vocal)<\/li>\n<li>i\u00f1aki \u00e1lvarez p\u00e9rez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Carmen Patricia Gomez Molina Hla-b27 is strongly associated with a group of rheumatic diseases collectively designed as 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