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HLA-associated susceptibility to childhood B-cell precursor ALL: definition and role of HLA-DPB1 supertypes.
Taylor, G M; Hussain, A; Lightfoot, T J; Birch, J M; Eden, T O B; Greaves, M F.
Afiliación
  • Taylor GM; School of Cancer Sciences, University of Manchester, Manchester, UK. gmtaylor@manchester.ac.uk
Br J Cancer ; 98(6): 1125-31, 2008 Mar 25.
Article en En | MEDLINE | ID: mdl-18334973
Childhood B-cell precursor (BCP) ALL is thought to be caused by a delayed immune response to an unidentified postnatal infection. An association between BCP ALL and HLA class II (DR, DQ, DP) alleles could provide further clues to the identity of the infection, since HLA molecules exhibit allotype-restricted binding of infection-derived antigenic peptides. We clustered >30 HLA-DPB1 alleles into six predicted peptide-binding supertypes (DP1, 2, 3, 4, 6, and 8), based on amino acid di-morphisms at positions 11 (G/L), 69 (E/K), and 84 (G/D) of the DPbeta(1) domain. We found that the DPbeta11-69-84 supertype GEG (DP2), was 70% more frequent in BCP ALL (n=687; P<10(-4)), and 98% more frequent in cases diagnosed between 3 and 6 years (P<10(-4)), but not <3 or >6 years, than in controls. Only one of 21 possible DPB1 supergenotypes, GEG/GKG (DP2/DP4) was significantly more frequent in BCP ALL (P=0.00004) than controls. These results suggest that susceptibility to BCP ALL is associated with the DP2 supertype, which is predicted to bind peptides with positively charged, nonpolar aromatic residues at the P4 position, and hydrophobic residues at the P1 and P6 positions. Studies of peptide binding by DP2 alleles could help to identify infection(s) carrying these peptides.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Predisposición Genética a la Enfermedad Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Male / Newborn Idioma: En Revista: Br J Cancer Año: 2008 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Predisposición Genética a la Enfermedad Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Child / Child, preschool / Female / Humans / Male / Newborn Idioma: En Revista: Br J Cancer Año: 2008 Tipo del documento: Article Pais de publicación: Reino Unido