Harris D P, Vordermeier H M, Arya A, Bogdan K, Moreno C, Ivanyi J
Tuberculosis and Related Infections Unit, Hammersmith Hospital, London, UK.
Immunology. 1996 Jul;88(3):348-54. doi: 10.1046/j.1365-2567.1996.d01-673.x.
The epitope specificity of T-cell help to B cells and of surface immunoglobulin-mediated B-cell-binding of antigens usually involves topographically distinct antigenic determinants. The possibility of cross-recognition of the same peptide sequence by both T cells and antibodies has been a matter of conflicting opinions. We investigated this subject by detailed mapping of T- and B-cell epitopes within four immunogenic mycobacterial peptides. The identified core sequences of T- and B-cell epitopes showed different topology within each peptide: they were partially overlapping or adjacent in two P38-derived peptides, but entirely overlapping in two P19-derived peptides. The critically important result using the two truncated peptides (P19/67-78 and P19/146-155) containing only the fully overlapping epitope cores was, that they retained full potency for inducing antibody responses. However, despite this desirable overlap of determinants, antipeptide sera failed to block the proliferation of corresponding T-cell hybridomas. We conclude, that our study, in contrast to previous findings, suggests that overlapping topology of T- and B-cell epitopes within synthetic peptides does not necessarily impair B-cell immunogenicity.
T细胞对B细胞的辅助作用以及表面免疫球蛋白介导的B细胞对抗原的结合作用,其表位特异性通常涉及拓扑结构不同的抗原决定簇。T细胞和抗体对同一肽序列进行交叉识别的可能性一直存在争议。我们通过详细绘制四种免疫原性分枝杆菌肽内的T细胞和B细胞表位来研究这一课题。所确定的T细胞和B细胞表位的核心序列在每种肽内显示出不同的拓扑结构:在两条源自P38的肽中它们部分重叠或相邻,但在两条源自P19的肽中则完全重叠。使用仅包含完全重叠表位核心的两条截短肽(P19/67 - 78和P19/146 - 155)得出的至关重要的结果是它们保留了诱导抗体反应的全部效力。然而,尽管决定簇有这种理想的重叠,但抗肽血清未能阻断相应T细胞杂交瘤的增殖。我们得出结论,与先前的发现相反,我们的研究表明合成肽内T细胞和B细胞表位的重叠拓扑结构不一定会损害B细胞的免疫原性。