Lehner T, Walker P, Bergmeier L A, Haron J A
Department of Immunology, United Medical School of Guy's Hospital, London, UK.
J Immunol. 1989 Oct 15;143(8):2699-705.
The immunogenicity and antigenicity of synthetic peptides (SP) derived from the sequences of a cell surface Ag of Streptococcus mutans were investigated in macaque monkeys. Immunization with the free peptides of 11, 17, and 21 residues failed to elicit serum antibodies or T cell responses. However, immunization with the SP17 and SP21 linked to tetanus toxoid (TT) as a carrier elicited serum antibodies and proliferative responses of lymphocytes, not only to the SP but also to the native streptococcal Ag. In vivo recall of SP-TT immunized monkeys with suboptimal doses of the native streptococcal Ag resulted in a significant increase in antibodies, both to the SP and the streptococcal Ag, confirming that the SP shares antigenic epitopes with the native Ag. B and T cell epitopes were then determined and a B cell epitope was found in residues 8-13, whereas an overlapping T cell epitope was located in residues 7-15. The T cell epitope has an amino-terminal leucine and carboxy-terminal glycine and alanine added to residues 8-13 of the B cell epitope. In spite of the B and T cell epitopes being expressed in SP17 (residues 1-15), the monomer failed to induce serum antibodies without a carrier. However, immunization with a dimer of SP17 elicited both serum antibodies and proliferative responses of lymphocytes without a carrier. The results suggest that the monomeric SP17 is not immunogenic and needs to be dimerised in order to elicit antibodies and T cell responses, both to the SP and to the streptococcal Ag.
对源自变形链球菌细胞表面抗原序列的合成肽(SP)在猕猴体内的免疫原性和抗原性进行了研究。用11、17和21个残基的游离肽进行免疫未能引发血清抗体或T细胞反应。然而,用与破伤风类毒素(TT)连接作为载体的SP17和SP21进行免疫,不仅引发了针对SP的血清抗体和淋巴细胞增殖反应,还引发了针对天然链球菌抗原的反应。用次优剂量的天然链球菌抗原对经SP-TT免疫的猴子进行体内再次刺激,导致针对SP和链球菌抗原的抗体显著增加,证实SP与天然抗原有共同的抗原表位。随后确定了B细胞和T细胞表位,在8-13位残基中发现了一个B细胞表位,而一个重叠的T细胞表位位于7-15位残基。T细胞表位在B细胞表位的8-13位残基上添加了氨基末端亮氨酸和羧基末端甘氨酸及丙氨酸。尽管B细胞和T细胞表位在SP17(1-15位残基)中表达,但单体在没有载体的情况下未能诱导血清抗体。然而,用SP17二聚体进行免疫在没有载体的情况下引发了血清抗体和淋巴细胞增殖反应。结果表明,单体SP17没有免疫原性,需要二聚化才能引发针对SP和链球菌抗原的抗体及T细胞反应。