Research School of Biology, Australian National University, Canberra, Australian Capital Territory, Australia.
J Immunol. 2010 Jan 1;184(1):45-55. doi: 10.4049/jimmunol.0900999. Epub 2009 Nov 30.
Previous studies of CD8(+) T cell immunodominance after primary virus infection of F(1) mice compared with their inbred parents have generally concluded that no dramatic changes occur. In this study, we revisit this issue using vaccinia virus (VACV), which has a large genome, a recently defined immunodominance hierarchy in mice, and is a candidate vector for vaccines. We found that immunogenicity of VACV peptides defined using inbred mice was highly variable in F(1) progeny: some peptides were equally immunogenic in F(1) and inbred, whereas others elicited responses that were reduced by >90% in F(1) mice. Furthermore, the dominance of a peptide in the relevant inbred parent did not predict whether it would be poorly immunogenic in F(1) mice. This result held using F(1) hybrids of MHC-congenic mice, suggesting that MHC differences alone were responsible. It was also extended to foreign epitopes expressed by an rVACV vaccine. F(1) mice were less able to mount responses to the poorly immunogenic peptides when used as a sole immunogen, ruling out immunodomination. In addition, conserved TCR Vbeta usage between inbred and F(1) mice did not always correlate with strong responses in F(1) mice. However, direct estimation of naive precursor numbers showed that these were reduced in F(1) compared with inbred mice for specificities that were poorly immunogenic in the hybrids. These data have implications for our understanding of the extent to which MHC diversity alters the range of epitopes that are immunogenic in outbred populations.
先前的研究比较了 F1 代小鼠与近交系父母在初次病毒感染后 CD8(+)T 细胞免疫优势，普遍认为没有明显变化。在这项研究中，我们使用痘苗病毒（VACV）重新研究了这个问题，VACV 基因组较大，在小鼠中有明确的免疫优势等级，并且是疫苗的候选载体。我们发现，使用近交系小鼠定义的 VACV 肽的免疫原性在 F1 后代中高度可变：一些肽在 F1 和近交系中具有同等的免疫原性，而其他肽在 F1 小鼠中的反应降低了>90%。此外，相关近交系亲本中肽的优势并不能预测其在 F1 小鼠中是否免疫原性差。这一结果在 MHC 同系小鼠的 F1 杂交中得到了验证，表明仅 MHC 差异是造成这种情况的原因。它也扩展到了 rVACV 疫苗表达的外来表位。当用作唯一免疫原时，F1 小鼠对免疫原性差的肽产生反应的能力降低，排除了免疫优势。此外，近交系和 F1 小鼠之间保守的 TCR Vbeta 使用并不总是与 F1 小鼠中的强反应相关。然而，直接估计幼稚前体数量表明，对于在杂种中免疫原性差的特异性，F1 小鼠中的这些数量比近交系小鼠减少。这些数据对于我们理解 MHC 多样性在多大程度上改变了在外群中免疫原性的表位范围具有重要意义。
