Immune Netw.  2014 Aug;14(4):219-225. 10.4110/in.2014.14.4.219.

Relationship between Poor Immunogenicity of HLA-A2-Restricted Peptide Epitopes and Paucity of Naive CD8+ T-Cell Precursors in HLA-A2-Transgenic Mice

• Choi YS
• Lee DH
• Shin EC

• KMID: 2150810
• DOI: http://doi.org/10.4110/in.2014.14.4.219

Abstract

We examined the immunogenicity of H-2 class I-restricted and HLA-A2-restricted epitopes through peptide immunization of HLA-A2-transgenic mice that also express mouse H-2 class I molecules. All four of the tested epitopes restricted by H-2 class I robustly elicited T-cell responses, but four of seven epitopes restricted by HLA-A2 did not induce T-cell responses, showing that HLA-A2-restricted peptide epitopes tend to be poorly immunogenic in HLA-A2-transgenic mice. This finding was confirmed in HLA-A2-transgenic mice infected with a recombinant vaccinia virus expressing hepatitis C virus proteins. We examined the precursor frequency of epitope-specific naive CD8+ T cells in HLA-A2-transgenic and conventional C57BL/6 mice and found that the poor immunogenicity of HLA-A2-restricted peptide epitopes is related to the paucity of naive CD8+ T-cell precursors in HLA-A2-transgenic mice. These results provide direction for the improvement of mouse models to study epitope repertoires and the immunodominance of human T-cell responses.

Keyword

CD8+ T cells; T cell immunogenicity; T cell epitope; Major histocompatibility complex class I; HLA-A2; Naive T cell precursor

MeSH Terms

Animals
Epitopes*
Epitopes, T-Lymphocyte
Hepacivirus
HLA-A2 Antigen
Humans
Immunization
Mice*
Precursor Cells, T-Lymphoid*
T-Lymphocytes
Vaccinia virus
Epitopes
Epitopes, T-Lymphocyte
HLA-A2 Antigen

Figure

• 

  Figure 1 Immunogenicity of H-2 class I-restricted and HLA-A2-restricted peptide epitopes in HLA-A2-transgenic mice. (A) HLA-A2-transgenic mice were immunized with peptide epitopes, and epitope-specific T-cell responses were evaluated with direct ex vivo interferon gamma (IFN-γ) ELISPOT assays with splenocytes as described in Materials and Methods (n=3-5). (B) HLA-A2-transgenic mice were immunized with peptide epitopes, and MHC class I pentamer staining was performed with splenocytes as described in Materials and Methods. (C) HLA-A2-transgenic mice were infected with recombinant vaccinia virus-hepatitis C virus (rVV-HCV)NS3-4B, and epitope-specific T-cell responses were evaluated with direct ex vivo IFN-γ ELISPOT assays with splenocytes as described in Materials and Methods (n=5; **p<0.01).

• 

  Figure 2 Precursor frequency of epitope-specific naïve CD8+ T cells. Cells were isolated from the secondary lymphoid organs of the whole body of an HLA-A2-transgenic (A) or C57BL/6 (B) mouse and stained with MHC class I pentamer. MHC class I pentamer(+) cells were magnetically enriched and detected with flow cytometry. The precursor frequency of epitope-specific naïve CD8+ T cells was calculated as described in Materials and Methods.

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