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Flexibility in T‐cell receptor ligand repertoires depends on MHC and T‐cell receptor clonotype
Author(s) -
GELUK A.,
MEIJGAARDEN K. E.,
OTTENHOFF T. H. M.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.1997.00370.x
Subject(s) - t cell receptor , major histocompatibility complex , biology , allorecognition , mhc restriction , epitope , t cell , human leukocyte antigen , molecular mimicry , peptide , antigen presentation , receptor , antigen , cd8 , microbiology and biotechnology , immunology , genetics , immune system , biochemistry
SUMMARY 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.