Perkins D L, Wang Y S, Fruman D, Seidman J G, Rimm I J
Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital, Boston, MA 02115.
J Immunol. 1991 May 1;146(9):2960-4.
Despite the tremendous plasticity of the TCR repertoire, T cells recognize a limited number of antigenic sites (frequently a single site, or immunodominant epitope) on a complex protein Ag. Current models suggest that the immunodominant epitope of a complex protein is the processed peptide that binds to the MHC molecule with the highest affinity. Conversely, the inability of the T cell population to recognize a specific epitope, termed a "hole" in the repertoire, can prevent the immunodominance of a peptide despite efficient processing and MHC binding of the peptide. The role of specific TCR alpha- or beta-chains in determining MHC restriction and recognizing specific epitopes is complex and incompletely understood. To evaluate the contribution of each TCR chain to the functional diversity of the T cell repertoire, we investigated in vivo the T cell response to phage lambda-repressor protein in transgenic mice expressing a single rearranged beta-chain gene (C57L beta mice) in association with the complete germline alpha-chain repertoire. Our results demonstrate that expression of the TCR beta-chain transgene alters the immunodominant epitope recognized by T cells. However, after immunization with the appropriate peptide the transgenic mice can also respond to the nonimmunodominant epitope; thus, the expression of the TCR beta-chain transgene does not create a hole in the repertoire. These data indicate that the primary site, or immunodominant epitope, of an Ag recognized by T cells can be altered by the preimmune TCR repertoire independent of antigen processing and MHC affinity.
尽管TCR库具有巨大的可塑性，但T细胞识别复杂蛋白质抗原上有限数量的抗原位点（通常是单个位点或免疫显性表位）。目前的模型表明，复杂蛋白质的免疫显性表位是与MHC分子结合亲和力最高的加工肽。相反，T细胞群体无法识别特定表位（即库中的“漏洞”），尽管该肽能够有效加工并与MHC结合，但仍可阻止该肽的免疫显性。特定的TCRα链或β链在决定MHC限制性和识别特定表位方面的作用复杂且尚未完全了解。为了评估每条TCR链对T细胞库功能多样性的贡献，我们在体内研究了表达单个重排β链基因的转基因小鼠（C57Lβ小鼠）与完整种系α链库相关联时对噬菌体λ阻遏蛋白的T细胞反应。我们的结果表明，TCRβ链转基因的表达改变了T细胞识别的免疫显性表位。然而，用适当的肽免疫后，转基因小鼠也能对非免疫显性表位作出反应；因此，TCRβ链转基因的表达不会在库中产生漏洞。这些数据表明，T细胞识别的抗原的主要位点或免疫显性表位可被免疫前TCR库改变，而与抗原加工和MHC亲和力无关。
