Langton B C, Mackewicz C E, Wan A M, Andria M L, Benjamini E
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis 95616.
J Immunol. 1988 Jul 15;141(2):447-56.
The protein Ag, tobacco mosaic virus protein, (TMVP) and its tryptic peptide number 8 (residues 93-112 of the protein) exhibit cross-reactivity on the T cell level in some strains of mice (e.g., C3H.SW, C57BL/10); these strains are termed cross-reactive (CR). In other strains such as A/J or B10.BR, no cross-reactivity is exhibited; these strains are termed non-cross-reactive (NCR). Genetic experiments indicated that the cross-reactivity is dominant and that it is mapped to the I-A or I-E region of the MHC, with cross-reactivity exhibited by the I-Ab haplotype but not by I-Ak or I-Ek. Cell reconstitution experiments have indicated that the non-cross-reactivity is associated with the inability of the NCR APC to present Ag. Analysis of the area(s) on peptide 8 which serve(s) as epitope revealed that both strains recognize an overlapping area consisting of 11 amino acid residues in the middle of peptide 8 (residues 97-107), which by itself is nonstimulatory to TMVP- or peptide 8-immune T cells of the CR or the NCR strains. However, the addition of a few amino acid residues of the sequence of peptide 8 to this area converts it to a complete stimulatory epitope. Additivity experiments revealed that the CR strain contains two major T cell populations each recognizing this middle region of peptide 8 when elongated by a few amino acids N-terminally and C-terminally, respectively. In contrast, the NCR strain contains one major T cell population recognizing elongation only N-terminally. Because TMVP (but not peptide 8) requires processing before presentation to T cells, it is postulated that, during processing of TMVP, there occur alterations in the area of the proximal three or four N-terminal amino acids of the region consisting of peptide 8, destroying the only region containing the T cell epitope recognized by the NCR strain, hence TMVP and peptide 8 do not exhibit cross-reactivity in this strain. The same alterations of TMVP still leave intact an epitope consisting of amino acid residues C-terminal to the altered area which is recognized by the CR strain, hence the cross-reactivity exhibited by this strain. The results suggest that the difference in cross-reactivity on the T cell level between TMVP and peptide 8 exhibited by the strains may be due to differences in the orientation of presentation and the subsequent cell recognition of an epitope contained within peptide 8.(ABSTRACT TRUNCATED AT 400 WORDS)
蛋白质Ag，即烟草花叶病毒蛋白（TMVP）及其胰蛋白酶肽8（该蛋白的第93 - 112位氨基酸残基）在某些小鼠品系（如C3H.SW、C57BL/10）的T细胞水平上表现出交叉反应性；这些品系被称为交叉反应性（CR）品系。在其他品系如A/J或B10.BR中，则未表现出交叉反应性；这些品系被称为非交叉反应性（NCR）品系。遗传学实验表明，交叉反应性是显性的，并且它被定位到MHC的I - A或I - E区域，I - Ab单倍型表现出交叉反应性，而I - Ak或I - Ek则不表现。细胞重建实验表明，非交叉反应性与NCR抗原呈递细胞（APC）呈递Ag的无能有关。对作为表位的肽8上的区域进行分析发现，两个品系都识别肽8中间由11个氨基酸残基组成的重叠区域（第97 - 107位氨基酸残基），该区域本身对CR或NCR品系的TMVP或肽8免疫T细胞无刺激作用。然而，向该区域添加肽8序列的几个氨基酸残基可将其转化为一个完整的刺激表位。加性实验表明，CR品系包含两个主要的T细胞群体，每个群体分别识别肽8中间区域在N端和C端延伸几个氨基酸后的区域。相比之下，NCR品系包含一个主要的T细胞群体，仅识别N端的延伸。由于TMVP（但不是肽8）在呈递给T细胞之前需要加工，因此推测在TMVP加工过程中，由肽8组成的区域近端三或四个N端氨基酸区域会发生改变，破坏了NCR品系识别的唯一包含T细胞表位的区域，因此TMVP和肽8在该品系中不表现出交叉反应性。TMVP的相同改变仍使由改变区域C端的氨基酸残基组成的表位保持完整，该表位被CR品系识别，因此该品系表现出交叉反应性。结果表明，各品系在TMVP和肽8之间T细胞水平上交叉反应性的差异可能是由于肽8中所含表位的呈递方向以及随后的细胞识别差异所致。（摘要截断于400字）
