T Cell Activity Correlates with Oligomeric Peptide-Major Histocompatibility Complex Binding on T Cell Surface

Recognition of virally infected cells by CD8+ T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the rejection of transplanted organs from the same species (allotranspla...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-12, Vol.276 (50), p.47320-47328
Main Authors: Buslepp, Jennifer, Zhao, Rui, Donnini, Debora, Loftus, Douglas, Saad, Mohamed, Appella, Ettore, Collins, Edward J.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Biotinylation
Cell Membrane - metabolism
Crystallography, X-Ray
Dimerization
Dose-Response Relationship, Drug
Flow Cytometry
histocompatibility antigen H-2
histocompatibility antigen HLA
Histocompatibility Antigens Class I - metabolism
HLA-A2 Antigen - metabolism
Humans
Kinetics
Ligands
Mice
Models, Molecular
Molecular Sequence Data
Peptides - chemistry
Phenotype
Protein Binding
Protein Conformation
Recombinant Proteins - metabolism
Spectrometry, Fluorescence
T-Lymphocytes - metabolism
T-Lymphocytes, Cytotoxic - metabolism
Time Factors
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Summary:Recognition of virally infected cells by CD8+ T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the rejection of transplanted organs from the same species (allotransplant) or different species (xenotransplant). AHIII12.2 is a murine T cell clone that recognizes the xenogeneic (human) class I MHC HLA-A2.1 molecule (A2) and the syngeneic murine class I MHC H-2 Db molecule (Db). Recognition of both A2 and Db are peptide-dependent, and the sequences of the peptides recognized have been determined. Alterations in the antigenic peptides bound to A2 cause large changes in AHIII12.2 T cell responsiveness. Crystal structures of three representative peptides (agonist, null, and antagonist) bound to A2 partially explain the changes in AHIII12.2 responsiveness. Using class I pMHC octamers, a strong correlation is seen between T cell activity and the affinity of pMHC complexes for the T cell receptor. However, contrary to previous studies, we see similar half-lives for the pMHC multimers bound to the AHIII12.2 cell surface.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109231200