Flexibility in T-cell receptor ligand repertoires depends on MHC and T-cell receptor clonotype
| Autor: | A. Geluk, T. H. M. Ottenhoff, K. E. Van Meijgaarden |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Chaperonins
T-Lymphocytes Molecular Sequence Data Immunology Cell Culture Techniques Receptors Antigen T-Cell Epitopes T-Lymphocyte Hemagglutinins Viral chemical and pharmacologic phenomena Peptide Human leukocyte antigen Biology Major histocompatibility complex Epitope Structure-Activity Relationship Bacterial Proteins Humans Immunology and Allergy Amino Acid Sequence HLA-DR2 Antigen Receptor Allorecognition chemistry.chemical_classification T-cell receptor HLA-DR1 Antigen Chaperonin 60 HLA-DR Antigens MHC restriction Molecular biology Peptide Fragments Cell biology chemistry biology.protein Cell Division Research Article |
| Zdroj: | Immunology. 90:370-375 |
| ISSN: | 1365-2567 0019-2805 |
| DOI: | 10.1111/j.1365-2567.1997.00370.x |
| Popis: | T-cell receptors (TCR) recognize peptides complexed to self-major histocompatibility complex (MHC) molecules. Recognition of peptide/MHC ligands by the TCR is highly peptide specific. However, certain TCRs can also recognize sequence-related and -unrelated ('mimicry') epitopes presented by homologous MHC molecules. Using two human, human leucocyte antigen-DR1 (HLA-DR1)-restricted T-cell clones specific for HA p307-319, we identified several diverse combinations of peptide-MHC complexes that are functionally equivalent in their ability to trigger T-cell stimulation. These findings demonstrate that a single TCR can productively interact with different peptides complexed to self- as well as non-self-MHC molecules. This extended reactivity is human leucocyte antigen (HLA) allele and TCR clonotype dependent, as the peptide repertoire recognized depends on the presenting HLA-DR molecule and varies among different TCRs that both recognize the HA p307-319/DR1 complex. Importantly, certain peptide analogues can completely change the HLA-restriction pattern of the TCR: T-cell recognition of the wild-type peptide that was absent in the context of a non-self HLA-DR molecule, was restored by complementing substitutions in altered peptide ligands, that could not be presented by the original restriction element. This mechanism may play an important role in allorecognition. |
| Databáze: | OpenAIRE |
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