In the memory response to the phosphorylcholine hapten (PC) two major groups of anti-PC antibodies with different fine specificities are elicited. Group I antibodies are mainly PC specific, whereas Group II antibodies are comprised of two specificities directed against the phenyl-PC and the phenyl moiety of the PC hapten. The VL gene usage of 17 monoclonal memory anti-PC antibodies were investigated by Southern blot analysis and nucleotide sequencing. Six out of eight Group I memory PC-specific antibodies used the same VK22-JK5 rearrangement as the major T15 primary response idiotype. One expressed a mutated JK1 and one employed another VK22 gene family member. A shift in specificity from PC (Group I) towards phenyl-PC (Group II) was accompanied with the usage of either VK1C-JK1 or VK1A-JK5 rearrangements. The phenyl-specific Group II antibodies expressed the V lambda 1-J lambda 1 L chain rearrangement in combination with VH M141 expressing H chains. In this specific segment of Group II antibodies most mutations were found. Thus four different VL genes were found to contribute to the fine specificity of memory response antibodies to the PC hapten in a clear structure-function relationship. The diversified fine specificity in the memory response derives mainly from the usage of different L chains with particular VJ rearrangements in combination with VH of the dominant initial response clonotype and is not primarily due to mutational events.
Based on their fine specificity, two groups of antibodies against the phosphorylcholine (PC) hapten have been described. Group I antibodies react predominantly with the PC moiety of the hapten and group II are directed against the entire hapten including the azophenyl spacer to the protein carrier. We have analyzed the VH gene segment utilization of hybridomas from the memory response to PC by Southern blot analysis and nucleotide sequencing of the functional VDJ rearrangements. Three main specificities of anti-PC antibodies could be distinguished. Anti-PC hybridomas with group I fine specificity utilize the VH1-DFL 16.1-JH1 rearrangement. A major portion of group II antibodies recognized the phenyl-PC part and expressed the same VH1 gene in combination with a member of the SP2 family and JH1 or JH2. The other anti-PC antibodies either used the PJ14-DFL16-JH3 rearrangement in combination with a lambda 1 L chain or a member of the VGam3.8 VH family rearranged to the DFL16.1 and the JH3 gene segments. The PJ14 and VGam3.8 V gene expressing antibodies were directed to the phenyl group and were either not or barely inhibitable by PC chloride. Thus, specific VDJ gene combinations contribute to the fine specificity of antibodies in the memory response to the PC hapten. The use of the S107, Q52, and VGam3.8. VH gene families, together with FL16.1 or SP2 D segments and JH1, JH2, or JH3 results in different fine specificities to the PC, phenyl-PC, or the azophenyl moiety of the PC hapten. These fine specificities of the memory response use V, D, and J segments of the initial T15Id+ response in combination with gene segments usually related to phenyl specificity.
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