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Structural Differences Associated with the Cytotoxic T-cell Response to an Immunodominant Epitope of the Influenza A Virus

Nov 6, 2017 1:23:01 PM / by Stacy Matthews Branch, DVM, PhD

Chemical, biology, chemistry or medical labThe influenza A virus (IAV) is the cause of yearly seasonal flu epidemics and is eliminated by CD8+ cytotoxic T cells. Recognition of infected cells is mediated by T cell receptors composed of two (a and b) glycoprotein chains. These receptors bind viral peptides presented by major histocompatibility complex (MHC) class I molecules on infected cells. Cytotoxic T cell receptors that recognize GILGFVFTL (GIL), the immunodominant epitope of IAV, are produced in people who express the MHC class I molecule HLA-A2.


Studies of the CD8+ cytotoxic T cell responses in HLA-A2+ individuals have shown that the Vb (b-chain variable) repertoire is mainly coded by the TRBV19 gene, while the Va (a-chain variable) gene is coded mainly by TRAV27. The products of TRAV27/TRBV19 gene combinations are canonical (standard), recognize the featureless peptide epitope, and exists in HLA-A matched (but unrelated) individuals. Studies using high-throughput sequencing revealed a higher repertoire diversity of GIL-specific non-canonical T cell receptors.

Researchers studied the structural basis of the T-cell receptor response to the dominant IAV epitope by comparing the F50 (a non-canonical GIL-specific T cell receptor expressing the TRAV131/TRBV27) with the previously published complex formed by a canonical T cell receptor (JM22). CD8+ cytotoxic T cells were obtained from the peripheral blood of HLA-A2+ donors. The cells were then stimulated with the GIL peptide, and IAV GIL-specific F50 T-cell receptor was isolated.

Using surface plasmon resonance, the affinity of F50 for GIL-HLA-A2 was found to be weaker than that of the JM22. Both the F50–GIL and JM22-GIL interfaces are characterized by two hydrogen bonds; however, the JM22-GIL interface uses different residues than that for F50. Studying the binding mode revealed that F50 and JM22 bind the GIL–HLA-A2 complex at different angles. The notch between GIL and HLA-A2 a2 helix is filled by arginine for F50 and tryptophan for JM22. These data show that there are a number of structural differences that allow higher T cell receptor diversity and recognition of the same peptide allowing a wide-ranging response to IAV and protection against viral evasion of the immune system.

If your research requires cytotoxic T cells, contact the biomedical product specialists at HemaCare today at 877-310-0717. We offer high quality, customizable products to meet your needs.

Yang X, e. (2017). Structural basis for clonal diversity of the human T cell response to a dominant influenza virus epitope. - PubMed - NCBI Ncbi.nlm.nih.gov. Retrieved 1 November 2017, from https://www.ncbi.nlm.nih.gov/pubmed/28931605

Topics: Cytotoxic T Cells

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