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Role of flanking variable sequences in antigenicity of consensus regions of HIV gp120 for recognition by specific human T helper clones

✍ Scribed by Fabrizio Manca; John A. Habeshaw; Angus G. Dalgleish; Daniela Fenoglio; Giuseppina Li Pira; Eli E. Sercarz


Publisher
John Wiley and Sons
Year
1993
Tongue
English
Weight
540 KB
Volume
23
Category
Article
ISSN
0014-2980

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✦ Synopsis


Human T helper cells can discriminate among strain variants of HIV gp120 because of T cell clones recognizing non-conserved regions, as demonstrated with T cells from HIV-infected individuals and vaccinated volunteers and with primary T cell lines and clones obtained by in vitro immunization. To obtain a better definition of cross-reactions amongT cell determinants within HIVgp120 variants, we used a panel of analog peptides within residues 236-251 from the BRU, MN, SF2 and F W strain sequences to induce primary human T cell lines and clones. Different patterns of response were obtaind using each of the analog peptides, although they all share the consensus sequence 246-251. Clones recognizing this sequence were generated by priming with the BRU and RF analog peptides, but not with the SF2 analog peptide. SF2 did not induce any 242-245-specific clones, but only T cells recognizing the 236-240 sequence. A preferential response to residues 236-240 was obtained by priming with the BRU and SF2 peptides, but not with the MN and F W peptides.

These results suggest that although the analog peptides exhibit a high degee of homology and share a consensus of the C-terminal sequence (246-251), theT cell response to the conserved sequence 246-251 is controlled by flanking sequences. Therefore the presence of a shared sequence per se does not imply in vitro expansion of clones with that fine specificity, even though such clones are available within the naive repertoire and can be triggered by an analog peptide.