Abstract
The high frequency of alloreactive T cells is a major hindrance for transplantation; however, the molecular basis for alloreactivity remains elusive. We examined the I-Ep alloreactivity of a well-characterized Hb(64-76)/I-Ek-specific murine T cell. Using a combinatorial peptide library approach, we identified a highly stimulatory alloepitope mimic and observed that the recognition of the central TCR contact residues (P3 and P5) was much more flexible than that seen with Hb(64-76)/I-Ek, but still specific. Therefore, alloreactive T cells can recognize a self-peptide/MHC surface; however, the allogeneic MHC molecule changes the recognition requirements for the central region of the peptide, allowing a more diverse repertoire of ligands to be recognized.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CHO Cells
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Complementarity Determining Regions*
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Cricetinae
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Histocompatibility Antigens Class II / chemistry
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / immunology*
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Hybridomas
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Immunoglobulin alpha-Chains / immunology
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Isoantigens / immunology*
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Mice
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Models, Molecular
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Mutagenesis, Site-Directed
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Peptide Mapping
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Polymorphism, Genetic
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Protein Binding
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Protein Structure, Secondary*
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Receptors, Antigen, T-Cell / immunology*
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Structure-Activity Relationship
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T-Lymphocytes / immunology
Substances
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Complementarity Determining Regions
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Histocompatibility Antigens Class II
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I-E-antigen
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Immunoglobulin alpha-Chains
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Isoantigens
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Receptors, Antigen, T-Cell