Yadav Rajwardhan, Yoshimura Yoshitaka, Boesteanu Alina, Christianson Gregory J, Ajayi Wilfred U, Shashidharamurthy R, Stanic Aleksandar K, Roopenian Derry C, Joyce Sebastian
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
J Immunol. 2003 May 15;170(10):5133-42. doi: 10.4049/jimmunol.170.10.5133.
Minor histocompatibility (H) Ag disparities result in graft-vs-host disease and chronic solid allograft rejection in MHC-identical donor-recipient combinations. Minor H Ags are self protein-derived peptides presented by MHC class I molecules. Most arise as a consequence of allelic variation in the bound peptide (p) that results in TCR recognizing the p/MHC as foreign. We used a combinational peptide screening approach to identify the immune dominant H2K(b)-restricted epitope defining the mouse H4(b) minor H Ag. H4(b) is a consequence of a P3 threonine to isoleucine change in the MHC-bound peptide derived from epithelial membrane protein-3. This allelic variation also leads to phosphorylation of the H4(b) but not the H4(a) epitope. Further, ex vivo CD8(+) T lymphocytes bind phosphorylated Ag tetramers with high efficiency. Although we document the above process in the minor H Ag system, posttranslational modifications made possible by subtle amino acid changes could also contribute to immunogenicity and immune dominance in tumor immunotherapeutic settings.
微小组织相容性（H）抗原差异会导致在主要组织相容性复合体（MHC）相同的供体 - 受体组合中发生移植物抗宿主病和慢性实体同种异体移植排斥反应。微小H抗原是由MHC I类分子呈递的自身蛋白质衍生肽。大多数是由于结合肽（p）中的等位基因变异导致T细胞受体（TCR）将p/MHC识别为外来物而产生的。我们使用组合肽筛选方法来鉴定定义小鼠H4(b)微小H抗原的免疫显性H2K(b)限制性表位。H4(b)是MHC结合肽中从上皮膜蛋白-3衍生的第3位苏氨酸到异亮氨酸变化的结果。这种等位基因变异还导致H4(b)表位而非H4(a)表位发生磷酸化。此外，体外CD8(+) T淋巴细胞能高效结合磷酸化的抗原四聚体。尽管我们在微小H抗原系统中记录了上述过程，但微小氨基酸变化所带来的翻译后修饰也可能在肿瘤免疫治疗环境中对免疫原性和免疫显性产生影响。
