Bhardwaj V, Kumar V, Grewal I S, Dao T, Lehmann P V, Geysen H M, Sercarz E E
Department of Microbiology and Molecular Genetics, University of California at Los Angeles 90024.
J Immunol. 1994 Apr 15;152(8):3711-9.
Recent experiments have shown that during the course of chronic experimental allergic encephalomyelitis, there is a shift in the determinant hierarchy away from the dominant to other subdominant and cryptic self determinants. It was therefore of interest to define the pattern of dominance for mouse myelin basic protein in the three commonly used experimental allergic encephalomyelitis model strains of mice, i.e., B10.PL, SJL/J, and (SJL x B10.PL)F1. Our studies indicate that many cryptic determinants are demonstrable, which only activate T cells on injection as individual peptides and not with the native protein. The core amino acid residues of the various determinants are defined and range in size between 5 and 10 amino acids. Interestingly, there is a bias toward H-2u-restricted response vis-a-vis the H-2s-restricted response in the (SJL x B10.PL)F1 strain. The TCR V beta 8.2 gene segment was not predominantly used for responses to other determinants, although some B10.PL and (SJL x B10.PL)F1 cell lines expressed V beta 8.2 more than others. This study represents the most comprehensive analysis so far of the pattern of dominant and cryptic proliferative T cell determinants and their core sequences for mouse myelin basic protein.
最近的实验表明,在慢性实验性变应性脑脊髓炎病程中,决定簇层次发生了转变,从占主导地位的决定簇转向其他次主导和隐蔽的自身决定簇。因此,确定小鼠髓鞘碱性蛋白在三种常用的实验性变应性脑脊髓炎模型小鼠品系(即B10.PL、SJL/J和(SJL×B10.PL)F1)中的优势模式很有意义。我们的研究表明,许多隐蔽决定簇是可证明的,这些决定簇仅在作为单个肽注射时激活T细胞,而与天然蛋白一起注射时则不然。各种决定簇的核心氨基酸残基已确定,大小在5至10个氨基酸之间。有趣的是,在(SJL×B10.PL)F1品系中,相对于H-2s限制的反应,存在对H-2u限制反应的偏向性。TCR Vβ8.2基因片段在对其他决定簇的反应中并非主要被使用,尽管一些B10.PL和(SJL×B10.PL)F1细胞系比其他细胞系更多地表达Vβ8.2。这项研究是迄今为止对小鼠髓鞘碱性蛋白的显性和隐蔽增殖性T细胞决定簇模式及其核心序列进行的最全面分析。