B- and T-lymphocyte responses to an immunodominant epitope of human immunodeficiency virus

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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“…Schrier et at. [20] reported that a 26-mer gp4l peptide {aa 584-609). which included the whole sequence of our immunodominant 12-mcr gp41|8!…”

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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“…obtained from control sera. n = 132 n = 28 n = 160 [Wang et al, 1986;Gnann et al, 1987a;Gnann et al, 1987b;Smith et al, 1987;Narvanen et al, 1988;Schrier et al, 1988;Shafferman et al, 19891. Surprisingly, only 50% of the sera from HIV-1 infected Tanzanians recognized this epitope.…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, we selected synthetic peptides that represented variable and conserved regions of gp160 among different HIV-1 isolates. The peptides have been previously shown to define HIV-1 gp160 epitopes based on recognition by antibodies from HIV-1 infected individuals and/or inducing anti-HIV-1 gp160 responses when immunized into experimental animals [Chanh et al, 1986;Kennedy et al, 1986;Wang et al, 1986;Gnann et al, 1987aGnann et al, , 1987bHo et al, 1987;Palker et al, 1987Palker et al, , 1988Smith et al, 1987;Narvanen et al, 1988;Schrier et al, 1988;Dope1 et al, 1989;Schafferman et al, 1989;Cease, 1990;Warren et al, 19901. Reactivity of HIV-1 sera from Tanzania to peptides 425-448, 616-632, and 735-752 that define 1 gp120 and 2 gp41 epitopes, respectively, was shown to be weak (less than 6%).…”

Section: Discussionmentioning

confidence: 99%

Fine specificity of the humoral immune response to HIV‐1 GP160 in HIV‐1 infected individuals from tanzania

Nkya

Warren

Wolf

et al. 1992

Journal of Medical Virology

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A total of 160 sera from HIV-1 infected individuals from Tanzania were examined for their fine specificity characteristics relative to 9 synthetic peptides that define HIV-1 gp160 epitopes. Immunorecessive and immunodominant epitopes were identified in both gp120 and gp41 based on serologic reactivity of these HIV-1 infected sera. A significant difference in fine specificity among HIV-1 infected individuals from Tanzania and the United States was observed for an immunodominant gp41 epitope. No significant differences in reactivity among asymptomatic vs. symptomatic HIV-1 infected individuals were detected for the selected HIV-1 gp160 epitopes defined by these peptides. The majority of sera from HIV-1 infected Tanzanians contained antibodies that recognized a peptide corresponding to the V3 region of gp120 from the HIV-1 MN isolate. These data suggest that regional isolates of HIV-1 may exist in Tanzania that differ from HIV-1 isolated in the United States. However, based on serology, HIV-1 isolates exhibiting sequences with HIV-1 MN V3 similarity may also be prevalent in Tanzania. The results of this study may be useful for the design of more effective AIDS diagnostic and therapeutic products for use worldwide.

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“…As a result, enhanced asymmetry between conditions for immune stimulation and antigen removal facilitates elimination of pathogens. Conversely, pathogens evolve immunodominance [67] and make fitness-restoring mutations [68] that increase R act and decrease R inh , both of which aid in evasion.…”

Section: Discussionmentioning

confidence: 99%

Trait-space patterning and the role of feedback in antigen-immunity coevolution

Jiang

Wang

2019

Phys. Rev. Research

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Coevolutionary arms races form between interacting populations that constitute each other's environment and respond to mutual changes. This inherently far-from-equilibrium process finds striking manifestations in the adaptive immune system, where highly variable antigens and a finite repertoire of immune receptors coevolve on comparable timescales. This unique challenge to the immune system motivates general questions: How do ecological and evolutionary processes interplay to shape diversity? What determine the endurance and fate of coevolution? Here, we take the perspective of responsive environments and develop a phenotypic model of coevolution between receptors and antigens that both exhibit cross-reactivity (one-to-many responses). The theory predicts that the extent of asymmetry in cross-reactivity is a key determinant of repertoire composition: small asymmetry supports persistent large diversity, whereas strong asymmetry yields long-lived transients of quasispecies in both populations. The latter represents a new type of Turing mechanism. More surprisingly, patterning in the trait space feeds back on population dynamics: spatial resonance between the Turing modes breaks the dynamic balance, leading to antigen extinction or unrestrained growth. Model predictions can be tested via combined genomic and phenotypic measurements. Our work identifies cross-reactivity as an important regulator of diversity and coevolutionary outcome, and reveals the remarkable effect of ecological feedback in pattern-forming systems, which drives evolution toward non-steady states different than the Red Queen persistent cycles.

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B- and T-lymphocyte responses to an immunodominant epitope of human immunodeficiency virus

Cited by 77 publications

References 44 publications

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

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

Fine specificity of the humoral immune response to HIV‐1 GP160 in HIV‐1 infected individuals from tanzania

Trait-space patterning and the role of feedback in antigen-immunity coevolution

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