Yurin V L, Rudensky A Y, Mazel S M, Blechman J M
Laboratory of Immunology, All-Union Research Institute for Genetics, Moscow, USSR.
Eur J Immunol. 1989 Sep;19(9):1685-91. doi: 10.1002/eji.1830190924.
In the preceding report (Eur. J. Immunol. 1989. 19: 1677) we have demonstrated that normal B cells, including small B cells, are capable of presenting Ig kappa-1b allotypic determinants of their endogeneously synthesized Ig+ to Ig kappa-1b-immune major histocompatibility complex (MHC) class II-restricted T cells. A panel of Ig kappa-1b allotype-specific T cell clones from August rats has been developed to study further the presentation of self surface Ig by B cells from Ig kappa-1-congeneic August.1b rats. All the clones studied were of the T helper/inducer phenotype (W3/25+,OX8-) and restricted by the RT-1Bc molecule. These clones responded both to the serum IgG(Ig kappa-1b) in the presence of irradiated spleen cells (SC) from August rats and to the Ig kappa-1b-bearing irradiated B cells from August.1b rats. SC presentation of secreted IgG was much less effective than B cell presentation of membrane Ig. Using CNBr cleavage of isolated C kappa (Ig kappa-1b) domain followed by high-performance liquid chromatography fractionation of the derived antigenic peptides, the kappa chain sequence between amino acids 176 and 214 has been identified as the T cell epitope recognized by all T cell clones in association with RT-1Bc. The fragment 176-214 of the Ig kappa-1b allotype differs from that of Ig kappa-1a allotype by three amino acid substitutions at positions 184, 185, 188. T cell recognition of pL kappa-1b(176-214) required no additional processing by the antigen-presenting cell: the efficient presentation of the peptide but not of intact IgG(Ig kappa-1b) by the paraformaldehyde-fixed SC was observed. These data provide clear-cut evidence for an absolute requirement of the processing of Ig molecules for T cell recognition to occur in our experimental system. Although the fixation of B cells from August.1b rats diminished their Ig kappa-1b-presenting ability, fixed Ig kappa-1b+ B cells were still able to induce Ig kappa-1b-specific T cell clone responses. Our results suggest that B cells can express the processed form of self-synthesized surface Ig in addition to intact surface Ig molecules. The former can be recognized by MHC-restricted T cell.
在之前的报告(《欧洲免疫学杂志》1989年。19: 1677)中,我们已经证明正常B细胞,包括小B细胞,能够将其内源性合成的Ig⁺的Ig κ-1b同种异型决定簇呈递给Ig κ-1b免疫的主要组织相容性复合体(MHC)II类限制性T细胞。已从奥古斯特大鼠中培养出一组Ig κ-1b同种异型特异性T细胞克隆,以进一步研究来自Ig κ-1同基因的奥古斯特.1b大鼠的B细胞对自身表面Ig的呈递情况。所有研究的克隆均为辅助性T/诱导性表型(W3/25⁺,OX8⁻),并受RT-1Bc分子限制。这些克隆对来自奥古斯特大鼠的经辐照脾细胞(SC)存在时的血清IgG(Ig κ-1b)以及来自奥古斯特.1b大鼠的携带Ig κ-1b的经辐照B细胞均有反应。SC对分泌型IgG的呈递效果远不如B细胞对膜Ig的呈递。通过用溴化氰裂解分离的Cκ(Ig κ-1b)结构域,然后对衍生的抗原肽进行高效液相色谱分级分离,已确定氨基酸176至214之间的κ链序列为所有T细胞克隆与RT-1Bc结合识别的T细胞表位。Ig κ-1b同种异型的176 - 214片段与Ig κ-1a同种异型的片段在第184、185、188位有三个氨基酸替换。T细胞对pL κ-1b(176 - 214)的识别不需要抗原呈递细胞进行额外加工:观察到经多聚甲醛固定的SC能有效呈递该肽,但不能呈递完整的IgG(Ig κ-1b)。这些数据为在我们的实验系统中T细胞识别发生时对Ig分子加工的绝对需求提供了明确证据。尽管来自奥古斯特.1b大鼠的B细胞固定后其Ig κ-1b呈递能力降低,但固定的Ig κ-1b⁺ B细胞仍能诱导Ig κ-1b特异性T细胞克隆反应。我们的结果表明,B细胞除了能表达完整的表面Ig分子外,还能表达自身合成的表面Ig的加工形式。前者可被MHC限制性T细胞识别。