Beta-2-Microglobulin in Acquired Immune Deficiency Syndrome

Francioli, P.; François, Clément; Yersin, Bertrand; Schädelin, J; Mp, Glauser

doi:10.1159/000409715

Cited by 7 publications

(1 citation statement)

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“…Clinieians treating HIV-infected persons have found il difficult to reach consensus on which combination ofan array of frequently used surrogate markers will provide the most reliable data to predict a good or poor prognosis [ 12,16,[30][31][32]. Having identified this short and conserved-sequence HIV-derived synthetic peptide that consistently elicits cell-medialed immunity in asymptomatic patients only, we may now have al our disposal a lool wilh whieh lo predict the risk of disease progression in HiVinfected persons.…”

Section: Discussionmentioning

confidence: 99%

Definition of an immunodominant T cell epitope contained in the envelope gp41 sequence of HIV-1

Bell

Cooper

Kemp

et al. 1992

Clinical and Experimental Immunology

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SUMMARYThe majority of the immunodominant amino acid sequences of HIV-I that have been characterized to date are coded for by hypervariable gene sequences. These variable sequences are however interspersed with sequences that are highly conserved between HIV striiins. Inimunogenic viral products with amino acid sequences that vary minimally between strains, and that consistently elicit both humoral and cellular immune responses, may be ideal for inclusion in a subunit vaccine. We studied HiV-seronegative and HIV-infected persons, classified as asymptomatic (AS), ARC or AIDS, initially, we assessed the cellular immune status of each subject from results of T eel! phenotypc analyses, assays for serum levels of surrogate markers of disease progression, and responses to mitogens and recall antigen. In addition, we tested whether three short synthetic peptides derived from the conserved sequences of the envelope gp 120 (aa 262-284) and gp41 (aa 579-601), and core p 17 (aa 106-125) regions of the HTLV-I MB isolate, could elicit B cell as well as T cell responses in HlV-infected subjects. Only the gp41-derived sequence was immunogenic at both B and Tcell levels. To further characterize the gp4l epitope. we used a series of overlapping synthetic peptides derived from aeonserved region of the envelope gp41 (aa 572-613). We thus identified an immunodominant 12-mer peptide sequence. gp41 {8K«ia 593-604).. which consistently elicited both T cell blastogenic and Bceil (antibody) responses in AS HIV-seropositive individuals but not in ARC and AIDS patients. Linear regression analysis showed that in AS persons [here was a strong positive correlation (/'<0()0()5) between the absolute CD8 * Teell numbers and the magnitude of blastogenic responses to thegp41!81(aa 593 604). Furthermore, those AS subjeets with T cells that proliferated in response to this gp41 analogue also had significantly greater serum levels of antibody to the same short peptide sequence than symptomatic ARC and AIDS patients. These results suggest that cellular responses to ihe immunodominant and highly conserved envelope sequences of HIV-1, associated with increased CDS' T cells, may be important in the pathogenesis of HIV disease.

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