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Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy.

Siebold C, Hansen BE, Wyer JR, Harlos K, Esnouf RE, Svejgaard A, Bell JI, Strominger JL, Jones EY, Fugger L
Proc Natl Acad Sci U S A 101 1999-2004 (2004)
Cited: 110 times
EuropePMC logo PMID: 14769912

Abstract

The MHC class II molecule DQ0602 confers strong susceptibility to narcolepsy but dominant protection against type 1 diabetes. The crystal structure of DQ0602 reveals the molecular features underlying these contrasting genetic properties. Structural comparisons to homologous DQ molecules with differential disease associations highlight a previously unrecognized interplay between the volume of the P6 pocket and the specificity of the P9 pocket, which implies that presentation of an expanded peptide repertoire is critical for dominant protection against type 1 diabetes. In narcolepsy, the volume of the P4 pocket appears central to the susceptibility, suggesting that the presentation of a specific peptide population plays a major role.

Reviews - 1uvq mentioned but not cited (4)

  1. Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation. Wieczorek M, Abualrous ET, Sticht J, Álvaro-Benito M, Stolzenberg S, Noé F, Freund C. Front Immunol 8 292 (2017)
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Articles - 1uvq mentioned but not cited (38)

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  17. Microbes as Master Immunomodulators: Immunopathology, Cancer and Personalized Immunotherapies. Lérias JR, Paraschoudi G, de Sousa E, Martins J, Condeço C, Figueiredo N, Carvalho C, Dodoo E, Castillo-Martin M, Beltrán A, Ligeiro D, Rao M, Zumla A, Maeurer M. Front Cell Dev Biol 7 362 (2019)
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  21. The immunopathogenesis of narcolepsy type 1. Liblau RS, Latorre D, Kornum BR, Dauvilliers Y, Mignot EJ. Nat Rev Immunol (2023)

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  1. The spectrum of HLA-DQ and HLA-DR alleles, 2006: a listing correlating sequence and structure with function. Bondinas GP, Moustakas AK, Papadopoulos GK. Immunogenetics 59 539-553 (2007)
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  10. Human leukocyte antigen-DQ alleles and haplotypes and their associations with resistance and susceptibility to HIV-1 infection. Hardie RA, Luo M, Bruneau B, Knight E, Nagelkerke NJ, Kimani J, Wachihi C, Ngugi EN, Plummer FA. AIDS 22 807-816 (2008)
  11. Redundancy in antigen-presenting function of the HLA-DR and -DQ molecules in the multiple sclerosis-associated HLA-DR2 haplotype. Sospedra M, Muraro PA, Stefanová I, Zhao Y, Chung K, Li Y, Giulianotti M, Simon R, Mariuzza R, Pinilla C, Martin R. J. Immunol. 176 1951-1961 (2006)
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