Modification of peptide interaction with MHC creates TCR partial agonists
| Autor: | Brian D. Evavold, Chinh T. Dao, Kelli R. Ryan, Peter E. Jensen, Lisa K. McNeil |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
CD74
T-Lymphocytes Genes MHC Class II Immunology Dose-Response Relationship Immunologic Receptors Antigen T-Cell Epitopes T-Lymphocyte chemical and pharmacologic phenomena Peptide Moths Lymphocyte Activation Major histocompatibility complex Major Histocompatibility Complex Hemoglobins T-Lymphocyte Subsets MHC class I Animals Amino Acid Sequence Peptide sequence chemistry.chemical_classification MHC class II Molecular Structure biology T-cell receptor Cytochromes c MHC restriction Biochemistry chemistry biology.protein Insect Proteins Peptides |
| Zdroj: | Cellular Immunology. 227:70-78 |
| ISSN: | 0008-8749 |
| DOI: | 10.1016/j.cellimm.2004.01.003 |
| Popis: | We report the creation of TCR partial agonists by the novel approach of manipulating the interaction between immunogenic peptide and MHC. Amino acids at MHC anchor positions of the I-E(k)-restricted hemoglobin (64-76) and moth cytochrome c (88-103) peptides were exchanged with MHC anchor residues from the low affinity class II invariant chain peptide (CLIP), resulting in antigenic peptides with altered affinity for MHC class II. Several low affinity peptides were identified as TCR partial agonists, as defined by the ability to stimulate cytolytic function but not proliferation. For example, a peptide containing methionine substitutions at positions one and nine of the I-E(k) binding motif acted as a partial agonist for two hemoglobin-reactive T cell clones (PL.17 and 3.L2). The identical MHC anchor substitutions in moth cytochrome c (88-103) also created a partial agonist for a mCC-reactive T cell (A.E7). Thus, peptides containing MHC anchor modifications mediated similar T cell responses regardless of TCR fine specificity or antigen reactivity. This data contrasts with the unique specificity among individual clones demonstrated using traditional altered peptide ligands containing substitutions at TCR contact residues. In conclusion, we demonstrate that altering the MHC anchor residues of the immunogenic peptide can be a powerful method to create TCR partial agonists. |
| Databáze: | OpenAIRE |
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