HIV neutralizing IgA in exposed seronegative subjects recognise an epitope within the gp41 coiled-coil pocket

C. Pastori, C. Barassi, S. Piconi, R. Longhi, M. L. Villa, A. G. Siccardi, M. Clerici, L. Lopalco

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV)-specific IgA can be detected in cervical secretions, saliva, and sera of HIV-infected and HIV-uninfected individuals with a known exposure to the virus. IgA from HIV-uninfected exposed seronegative individuals (ESN) neutralize in vitro primary strains of HIV-1. We analyzed the epitopes of HIV recognized by serum HIV-specific IgA of ESN individuals to identify the antigenic correlates of HIV neutralization in exposed-uninfected subjects, and to verify whether different epitopes would be recognized by HIV-specific IgA of ESN and of HIV-infected patients. Results confirmed that HIV-neutralizing IgA are detected in sera of ESN and showed that neutralization of primary HIV strains is mediated by the recognition of different epitopes in HIV-infected patients and ESN. Thus, whereas IgA of HIV+ individuals recognize epitopes expressed both within gp120 and gp41, IgA of ESN exclusively bind to gp41-expressed epitopes. Epitope mapping revealed that the epitope recognized by serum IgA of ESN on gp41 is restricted to aa 581-584 (LQAR) and corresponds to coiled coil pocket in the αhelic region. In contrast, the epitope seen by IgA of HIV-infected patients on gp41 is identified by two regions; the first is contained within the cystein loop (aa 589-618), the second correspond to C terminal region in the extra membrane region of gp 41 (aa 642-673). Thus, we have identified and characterized the epitopes that mediate neutralization of HIV in individuals in whom infection does not occur despite multiple exposures to the virus. These results have important implications for the development of a new therapy against HIV infection.

Original languageEnglish
Pages (from-to)15-21
Number of pages7
JournalJournal of Biological Regulators and Homeostatic Agents
Volume14
Issue number1
Publication statusPublished - 2000

Fingerprint

Human immunodeficiency virus
neutralization
Immunoglobulin A
epitopes
Epitopes
HIV
Serum
Viruses
Epitope Mapping
viruses
HIV infections
neutralization tests
Human immunodeficiency virus 1
saliva
Virus Diseases
Saliva

Keywords

  • HIV infection
  • HIV neutralization
  • IgA
  • Mucosal immunity
  • Resistance

ASJC Scopus subject areas

  • Immunology
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Physiology (medical)
  • Medicine (miscellaneous)
  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

HIV neutralizing IgA in exposed seronegative subjects recognise an epitope within the gp41 coiled-coil pocket. / Pastori, C.; Barassi, C.; Piconi, S.; Longhi, R.; Villa, M. L.; Siccardi, A. G.; Clerici, M.; Lopalco, L.

In: Journal of Biological Regulators and Homeostatic Agents, Vol. 14, No. 1, 2000, p. 15-21.

Research output: Contribution to journalArticle

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