Rhipicephalus microplus lipocalins (LRMs): Genomic identification and analysis of the bovine immune response using in silico predicted B and T cell epitopes

Abstract Abstract 3175 Poster Board III-115 Administration of human Factor VIII to hemophilia A (FVIII-/-) mice is a useful small animal model to study the immune response in patients given therapeutic FVIII. These mice manifest a robust, T-cell dependent, antibody response to exogenous FVIII treatment even when encountered through traditionally tolerogenic routes, whereas a different foreign protein like ovalbumin (OVA) is much less immunogenic by these routes. Interestingly, administration of FVIII with OVA led to an immune response to both proteins, suggesting that the function of FVIII in the clotting cascade led to additional “danger” signals to co-administered proteins. Thus, we propose that FVIII is particularly immunogenic because of its function in the coagulation cascade that leads to thrombin formation. We showed that native FVIII is poorly immunogenic when it cannot activate downstream coagulation factors. Thus, heat-inactivated FVIII is poorly immunogenic despite containing normal T-cell epitopes. Importantly, native FVIII is less immunogenic in mice treated with warfarin (which blocks vitamin K-dependent enzymes) or with the direct thrombin-inhibitor, hirudin. Based on the hypothesis that thrombin generation is necessary for the immunogenicity and formation of inhibitors to FVIII, we wished to uncouple this immune response from the disease. When hemostatically normal BALB/c mice were injected directly with thrombin and OVA, they formed increased immune responses to OVA compared to mice given OVA alone. Thus, a likely mechanism is that FVIII treatment initiates a thrombin burst, which we propose is an immunogenic “danger” signal, leading indirectly to dendritic cell activation and promotion of an immune response. (Supported by NIH RO1 HL061883, NIH T32 HL007698, and AHA Fellowship 0815219E) Disclosures No relevant conflicts of interest to declare.

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Towards the in silico identification of class II restricted T-cell epitopes: a partial least squares iterative self-consistent algorithm for affinity prediction

Bioinformatics ◽

10.1093/bioinformatics/btg312 ◽

2003 ◽

Vol 19 (17) ◽

pp. 2263-2270 ◽

Cited By ~ 54

Author(s):

I.A. Doytchinova ◽

D.R. Flower

Keyword(s):

T Cell ◽

Least Squares ◽

Partial Least Squares ◽

In Silico ◽

Class Ii ◽

T Cell Epitopes ◽

Affinity Prediction ◽

Self Consistent ◽

In Silico Identification

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Long-Term Specific Immune Responses Induced in Humans by a Human Immunodeficiency Virus Type 1 Lipopeptide Vaccine: Characterization of CD8+-T-Cell Epitopes Recognized

Journal of Virology ◽

10.1128/jvi.77.20.11220-11231.2003 ◽

2003 ◽

Vol 77 (20) ◽

pp. 11220-11231 ◽

Cited By ~ 55

Author(s):

Hanne Gahéry-Ségard ◽

Gilles Pialoux ◽

Suzanne Figueiredo ◽

Céline Igéa ◽

Mathieu Surenaud ◽

...

Keyword(s):

Immune Response ◽

Human Immunodeficiency Virus ◽

T Cell ◽

T Cell Responses ◽

T Cell Epitopes ◽

Cell Responses ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT We studied the effect of booster injections and the long-term immune response after injections of an anti-human immunodeficiency virus type 1 (HIV-1) lipopeptide vaccine. This vaccine was injected alone or with QS21 adjuvant to 28 HIV-uninfected volunteers. One month later, after a fourth injection of the vaccine, B- and T-cell anti-HIV responses were detected in >85% of the vaccinated volunteers. One year after this injection, a long-term immune response was observed in >50% of the volunteers. At this point, a positive QS21 effect was observed only in the sustained B-cell and CD4+-T-cell responses. To better characterize the CD8+-T-cell response, we used a gamma interferon enzyme-linked immunospot method and a bank of 59 HIV-1 epitopes. For the six most common HLA molecules (HLA-A2, -A3, -A11, -A24, -B7 superfamily, and -B8), an average of 10 (range, 3 to 15) HIV-1 epitopes were tested. CD8+-T-cell responses were evaluated according to the HLA class I molecules of the volunteers. Each assessment was based on 18 HIV-1 epitopes in average. We showed that 31 HIV-1 epitopes elicited specific CD8+-T-cell responses after vaccination. The most frequently recognized peptides were Nef 68-76 (-B7), Nef 71-79 (-B7), Nef 84-92 (-A11), Nef 135-143 (-B7), Nef 136-145 (-A2), Nef 137-145 (-A2), Gag 259-267 (-B8), Gag 260-268 (-A2), Gag 267-274 (-A2), Gag 267-277 (-B7), and Gag 276-283 (A24). We found that CD8+-T-cell epitopes were induced at a higher number after a fourth injection (P < 0.05 compared to three injections), which indicates an increase in the breadth of HIV CD8+-T-cell epitope recognition after the boost.

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