Scott M G, Crimmins D L, McCourt D W, Chung G, Schäble K F, Thiebe R, Quenzel E M, Zachau H G, Nahm M H
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1991 Dec 1;147(11):4007-13.
We previously demonstrated that the human anti-Haemophilus influenzae type b polysaccharide (Hib-PS) VL repertoire is dominated by a product of the V kappa II gene, A2, and that V kappa II-A2 anti-Hib-PS antibodies have little or no somatic mutation in VL. To further study this VL repertoire, we studied non-A2 anti-Hib-PS antibodies that were identified either serologically or by amino-terminal amino acid sequence analysis. Of 15 non-A2 anti-Hib-PS antibodies from 12 vaccinated adults, we found four V lambda, five V kappa I, one non-A2 V kappa II, four V kappa III, and one V kappa IV antibodies. As expected, all but two of these subjects also produced V kappa II-A2 antibodies. Interestingly, one of these subjects lacks the A2 gene in the germ line. However, both subjects who did not produce detectable V kappa II antibody did produce normal amounts of total anti-Hib-PS antibody after vaccination. Candidate V kappa genes for the non-A2 antibodies were identified by comparison of up to 60 VL amino acid residues, including CDR1 and CDR2, with all sequenced V kappa genes. V kappa I antibodies appear to be products of three newly sequenced V kappa I genes, O8, O18, and L11, that are reported here. The O8 and O18 genes encode identical amino acid sequences. The non-A2 V kappa II antibody is a likely product of the A1 or A17 genes, the V kappa III antibodies are likely products of the A27 gene, and the V kappa IV antibody is a product of the single V kappa IV gene, B3. Unlike V kappa II-A2 antibodies, the V kappa I, V kappa III, and V kappa IV antibodies differed by one to five CDR residues from the germ line product of the candidate genes, suggesting the presence of somatic mutations. Thus, anti-Hib-PS antibodies can be divided into two types, the most frequently observed A2 antibodies with little or no somatic mutation and non-A2 antibodies that likely contain somatic mutations.
我们先前证明，人类抗b型流感嗜血杆菌多糖（Hib-PS）VL库主要由VκII基因A2的产物主导，并且VκII-A2抗Hib-PS抗体在VL中几乎没有或没有体细胞突变。为了进一步研究这个VL库，我们研究了通过血清学或氨基末端氨基酸序列分析鉴定的非A2抗Hib-PS抗体。在来自12名接种疫苗的成年人的15种非A2抗Hib-PS抗体中，我们发现了4种Vλ、5种VκI、1种非A2 VκII、4种VκIII和1种VκIV抗体。正如预期的那样，除了两名受试者外，其他所有受试者也产生了VκII-A2抗体。有趣的是，其中一名受试者在种系中缺乏A2基因。然而，两名未产生可检测到的VκII抗体的受试者在接种疫苗后确实产生了正常量的总抗Hib-PS抗体。通过将多达60个VL氨基酸残基（包括CDR1和CDR2）与所有已测序的Vκ基因进行比较，确定了非A2抗体的候选Vκ基因。VκI抗体似乎是这里报道的三个新测序的VκI基因O8、O18和L11的产物。O8和O18基因编码相同的氨基酸序列。非A2 VκII抗体可能是A1或A17基因的产物，VκIII抗体可能是A27基因的产物，VκIV抗体是单个VκIV基因B3的产物。与VκII-A2抗体不同，VκI、VκIII和VκIV抗体与候选基因的种系产物在1至5个CDR残基上存在差异，这表明存在体细胞突变。因此，抗Hib-PS抗体可分为两种类型，最常见的是几乎没有或没有体细胞突变的A2抗体和可能含有体细胞突变的非A2抗体。
