Cao W, Myers-Powell B A, Braciale T J
Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
J Immunol. 1996 Jul 15;157(2):505-11.
One of the two class I MHC (H-2Kd)-restricted immunogenic regions identified on the influenza virus strain A/Japan/57 (H2N2) hemagglutinin (HA) encompasses two distinct, partially overlapping epitopes. These epitopes map to residues 204 to 212 (JHA 204-212) and 210 to 219 (JHA 210-219), respectively. When we investigated the magnitude of the CTL responses of H-2d BALB/c mice to these two epitopes, we found that the JHA 204-212 nonamer epitope is immunodominant, eliciting vigorous CTL responses in BALB/c mice immunized with A/Japan/57 virus. In contrast, the CTL response to the JHA 210-219 decamer epitope was weak and variable. The subdominance of the JHA 210-219 was not due to low affinity binding of JHA 210-219 to H-2Kd or to inefficient processing of this epitope in vivo. Rather, an analysis of CTL precursor (pCTL) frequency by limiting dilution showed that the frequency of pCTL to the JHA 210-219 epitope was at least 10-fold lower than the frequency of pCTL to the JHA 204-212 epitope, implying that the low and variable response to the JHA 210-219 epitope was due to a limited number of CD8+ T cell precursors directed to JHA 210-219. This hypothesis was further supported by the finding of limited heterogeneity in reactivity pattern displayed by short term bulk cultures of the JHA 210-219-specific CTLs for cross-reactive epitopes. Implications of these findings for vaccine design and for T lymphocyte function and repertoire development are discussed.
在甲型流感病毒A/日本/57（H2N2）血凝素（HA）上鉴定出的两个I类主要组织相容性复合体（H-2Kd）限制性免疫原性区域之一，包含两个不同的、部分重叠的表位。这些表位分别对应于第204至212位氨基酸残基（JHA 204-212）和第210至219位氨基酸残基（JHA 210-219）。当我们研究H-2d BALB/c小鼠对这两个表位的细胞毒性T淋巴细胞（CTL）反应强度时，发现JHA 204-212九聚体表位具有免疫显性，在用A/日本/57病毒免疫的BALB/c小鼠中引发强烈的CTL反应。相比之下，对JHA 210-219十聚体表位的CTL反应较弱且不稳定。JHA 210-219的亚显性并非由于JHA 210-219与H-2Kd的低亲和力结合或该表位在体内加工效率低下。相反，通过有限稀释分析CTL前体（pCTL）频率表明，针对JHA 210-219表位的pCTL频率比对JHA 204-212表位的pCTL频率至少低10倍，这意味着对JHA 210-219表位的低反应性和不稳定反应是由于针对JHA 210-219的CD8 + T细胞前体数量有限。JHA 210-219特异性CTL短期大量培养物对交叉反应表位显示的反应模式异质性有限这一发现进一步支持了该假设。本文讨论了这些发现对疫苗设计以及T淋巴细胞功能和库发育的意义。
