Impact of HLA-B alleles, epitope binding affinity, functional avidity, and viral coinfection on the immunodominance of virus-specific CTL responses
| Autor: | Christian Brander, Tauheed Zaman, Eunice Pae, John Sidney, Tonia Woodberry, Nicole Frahm, Florian Bihl, Kaori Sango, Loriana Di Giammarino, Alessandro Sette, Karina Yusim, Bruce D. Walker, Mina John, John V. Chisholm, Hannah S. Hewitt, David Heckerman, Bette T. Korber, Leah M. Henry, Caitlyn Linde, Simon Mallal |
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| Předmět: |
Epstein-Barr Virus Infections
Herpesvirus 4 Human Molecular Sequence Data Immunology Epitopes T-Lymphocyte HLA-C Antigens Immunodominance Human leukocyte antigen Biology Epitope medicine HLA-B Antigens Humans Immunology and Allergy Avidity Amino Acid Sequence Alleles Acquired Immunodeficiency Syndrome HLA-A Antigens Immunodominant Epitopes medicine.disease Virology HLA-B CTL HIV-1 Coinfection T-Lymphocytes Cytotoxic |
| Zdroj: | Scopus-Elsevier |
| Popis: | Immunodominance is variably used to describe either the most frequently detectable response among tested individuals or the strongest response within a single individual, yet factors determining either inter- or intraindividual immunodominance are still poorly understood. More than 90 individuals were tested against 184 HIV- and 92 EBV-derived, previously defined CTL epitopes. The data show that HLA-B-restricted epitopes were significantly more frequently recognized than HLA-A- or HLA-C-restricted epitopes. HLA-B-restricted epitopes also induced responses of higher magnitude than did either HLA-A- or HLA-C-restricted epitopes, although this comparison only reached statistical significance for EBV epitopes. For both viruses, the magnitude and frequency of recognition were correlated with each other, but not with the epitope binding affinity to the restricting HLA allele. The presence or absence of HIV coinfection did not impact EBV epitope immunodominance patterns significantly. Peptide titration studies showed that the magnitude of responses was associated with high functional avidity, requiring low concentration of cognate peptide to respond in in vitro assays. The data support the important role of HLA-B alleles in antiviral immunity and afford a better understanding of the factors contributing to inter- and intraindividual immunodominance. |
| Databáze: | OpenAIRE |
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