Fine specificity analysis of an HLA-A2.1-restricted immunodominant T cell epitope derived from human α-fetoprotein
| Autor: | William H. McBride, Lisa H. Butterfield, Justin B. Heller, James S. Economou, John A. Glaspy, Antoni Ribas, Vivian B. Dissette, Wilson S. Meng |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Carcinoma Hepatocellular T-Lymphocytes T cell Immunology Receptors Antigen T-Cell Priming (immunology) Biology Lymphocyte Activation Major histocompatibility complex Epitope Mice Antigen HLA-A2 Antigen medicine Animals Humans Amino Acids Molecular Biology Alanine Immunodominant Epitopes Liver Neoplasms Molecular biology Peptide Fragments digestive system diseases medicine.anatomical_structure biology.protein Immunotherapy alpha-Fetoproteins Leucine Alpha-fetoprotein Oligopeptides |
| Zdroj: | Molecular Immunology. 37:943-950 |
| ISSN: | 0161-5890 |
| DOI: | 10.1016/s0161-5890(01)00017-7 |
| Popis: | Human alpha-fetoprotein (AFP) is a potentially important target for the immunotherapy of hepatocellular carcinoma (HCC). AFP(542-550) (GVALQTMKQ) is one of several HLA-A2.1-restricted immunodominant AFP peptides that consistently generate AFP-specific T cell responses in human T cell cultures and in HLA-A2.1/K(b) transgenic (A2.1 tg) mice. We performed a fine specificity analysis of this nonamer to determine which amino acid side chains were critical for T cell priming and recognition. Using peptide-pulsed dendritic cells (DC) as an immunization strategy, we characterized the effects of AFP(542-550) amino acid substitutions on priming and recognition in A2.1 tg mice. Replacing the glutamine at anchor position 9 with a leucine enhanced MHC binding and AFP-specific T cell responses. Substitution of leucine at non-anchor position 4 with an alanine did not alter binding but greatly diminished T cell recognition. Computer-generated three-dimensional models provided the structural rationale for these observed effects in MHC binding and T cell responses resulted from the modifications in the AFP(542-550) sequence. |
| Databáze: | OpenAIRE |
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