Evaluation of human histocompatibility leukocyte antigen (HLA) class II genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has shown a positive association with HLA-DRB1 alleles that contain Arg13 or Arg70-Arg71. Among TL patients, 87% carry specific alleles of DRB1 Arg13 or Arg70-Arg71 as compared to 43% among controls (p = 5 x 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, the side chains of which, when modeled on the DR1 crystal structure, line a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the binding cleft of an HLA molecule.
Article|
March 01 1996
Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy.
L Zerva,
L Zerva
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
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B Cizman,
B Cizman
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
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N K Mehra,
N K Mehra
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
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S K Alahari,
S K Alahari
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
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R Murali,
R Murali
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
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C M Zmijewski,
C M Zmijewski
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
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M Kamoun,
M Kamoun
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
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D S Monos
D S Monos
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
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L Zerva
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
B Cizman
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
N K Mehra
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
S K Alahari
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
R Murali
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
C M Zmijewski
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
M Kamoun
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
D S Monos
Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, 19104, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 183 (3): 829–836.
Citation
L Zerva, B Cizman, N K Mehra, S K Alahari, R Murali, C M Zmijewski, M Kamoun, D S Monos; Arginine at positions 13 or 70-71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy.. J Exp Med 1 March 1996; 183 (3): 829–836. doi: https://doi.org/10.1084/jem.183.3.829
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