tetano
Editor, Senior Moderator
J Virol. 2012 Sep 26. [Epub ahead of print]
Cross-allele CTL responses against 2009 pandemic H1N1 influenza A virus among HLA-A24 and HLA-A3 supertype-positive individuals.
Liu J, Zhang S, Tan S, Yi Y, Wu B, Cao B, Zhu F, Wang C, Wang H, Qi J, Gao GF.
Source
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.
Abstract
Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens to be presented by most, if not all, of the HLAs. Herein, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24(+) population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11(+) and HLA-A24(+) donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30) restricted manner. The cross-alelle antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the MHC/peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11(+) population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidated the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.
PMID:
23015716
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23015716
Cross-allele CTL responses against 2009 pandemic H1N1 influenza A virus among HLA-A24 and HLA-A3 supertype-positive individuals.
Liu J, Zhang S, Tan S, Yi Y, Wu B, Cao B, Zhu F, Wang C, Wang H, Qi J, Gao GF.
Source
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.
Abstract
Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens to be presented by most, if not all, of the HLAs. Herein, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24(+) population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11(+) and HLA-A24(+) donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30) restricted manner. The cross-alelle antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the MHC/peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11(+) population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidated the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.
PMID:
23015716
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23015716