How peptide-major histocompatibility complex (MHC) class II complexes are naturally generated is still unknown, but accumulating evidence suggests that unfolding proteins or long peptides can become bound to class II molecules at the dominant determinant before proteolytic cleavage. We have compared the immunogenicity of hen egg-white lysozyme (HEL) in nonobese diabetic (NOD), (NOD x BALB/c)F1, and E(d) alpha transgenic NOD mice. We find that a response to the subdominant ANOD-restricted determinant disappears upon introduction of an E(d) molecule, and is restored when scission of HEL separates this determinant from its adjoining, competitively dominant, E(d)-restricted determinant. This suggests that the E(d) molecule binds and protects its dominant determinant on a long peptide while captured neighboring determinants are lost during proteolysis. These results provide clear evidence for "determinant capture" as a mechanism of determinant selection during antigen processing and a possible explanation for MHC-protective effects in insulin-dependent diabetes mellitus.
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1 November 1993
Article|
November 01 1993
Determinant capture as a possible mechanism of protection afforded by major histocompatibility complex class II molecules in autoimmune disease.
H Deng,
H Deng
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
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R Apple,
R Apple
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
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M Clare-Salzler,
M Clare-Salzler
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
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S Trembleau,
S Trembleau
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
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D Mathis,
D Mathis
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
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L Adorini,
L Adorini
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
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E Sercarz
E Sercarz
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
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H Deng
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
R Apple
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
M Clare-Salzler
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
S Trembleau
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
D Mathis
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
L Adorini
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
E Sercarz
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024-1489.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1993) 178 (5): 1675–1680.
Citation
H Deng, R Apple, M Clare-Salzler, S Trembleau, D Mathis, L Adorini, E Sercarz; Determinant capture as a possible mechanism of protection afforded by major histocompatibility complex class II molecules in autoimmune disease.. J Exp Med 1 November 1993; 178 (5): 1675–1680. doi: https://doi.org/10.1084/jem.178.5.1675
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