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Major CD4 epitopes involved in anti-CD4 T-cell autoimmunity in HIV-1 patients
Rivka Abulafia-Lapid1, Yael Keren-Zur, Yulia Yachnin
1The Human Biology Research Center (HBRC), Hadassah University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel. rivka_abulafia@yahoo.com
Insights
HIV infection triggers T-cell responses to CD4. Synthetic CD4 peptides may offer a cost-effective T-cell vaccination strategy for HIV-positive patients with anti-CD4 autoimmunity.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- HIV infection can alter immune responses.
- T-cell reactivity to self-antigens like CD4 is a concern in autoimmune conditions.
Purpose of the Study:
- To investigate T-cell reactivity to CD4 in HIV-positive and HIV-negative individuals.
- To identify specific CD4 epitopes responsible for T-cell responses in HIV infection.
- To explore the potential of synthetic CD4 peptides for therapeutic vaccination.
Main Methods:
- Studied T-cell proliferation responses to recombinant CD4 (rCD4) in HIV-positive patients and controls.
- Mapped immunogenic CD4 epitopes using 31 overlapping synthetic peptides.
- Compared T-cell responses to specific peptides between infected and control groups.
Main Results:
- 80% of HIV-infected patients showed T-cell proliferation to rCD4, compared to 25% of controls.
- HIV-infected patients exhibited significantly higher responses to peptides p1, p4, p14, p21, p28, and p29.
- Peptides p1, p28, and p29 were identified as major immunogenic epitopes in HIV-infected individuals.
Conclusions:
- HIV infection is associated with increased T-cell reactivity to CD4.
- Synthetic CD4 peptides could be a basis for cost-effective T-cell vaccination in HIV-positive patients with anti-CD4 autoimmunity.
- Development of complementary TCR peptides for future vaccinations is suggested.
Abstract:
We studied HIV-positive and -negative subjects for T-cell reactivity to rCD4, and found that 80% of 25 tested HIV-infected patients and 25% of controls manifested T-cell proliferation responses to rCD4. We mapped the major CD4 immunogenic epitopes among the CD4+ responders of both groups by testing T-cell proliferation responses to 31 synthetic overlapping peptides from the human CD4 molecule. Such responses to p1, p4, p14, p21, p28 and p29 were significantly higher in the eight infected patients and, with the exception of p14, these peptides differed from those found in three HIV-negative controls (p11, p14 and p27). Peptides p1, p28 and p29 are major immunogenic epitopes. Our findings suggest: (1) that HIV infection is associated with T-cell reactivity to CD4; and (2) that the use of synthetic CD4 peptides to replace the complete CD4 molecule may therefore lead to a cost-effective T-cell vaccination for HIV-positive patients exhibiting anti-CD4 autoimmunity, as well as to the development of complimentary TCR peptides for future peptide vaccinations.
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