Mhc-i-restricted presentation of hiv-1 virion antigens...

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A61K 39/21 (2006.01) C07K 14/15 (2006.01) C07K 14/155 (2006.01) C07K 14/16 (2006.01) C12N 7/04 (2006.01) G01N 33/50 (2006.01) G01N 33/567 (2006.01)

Patent

CA 2439188

Dendritic cells and macrophages can process extracellular antigens for presentation by MHC-I molecules. HIV-1 epitopes derived from incoming virions are presented through the exogenous MHC-I pathway in primary human dendritic cells, and to a lower extent in macrophages, leading to cytotoxic T lymphocyte activation in the absence of viral protein neosynthesis. Exogenous antigen presentation required adequate virus-receptor interactions and fusion of viral and cellular membranes. These results provide new insights about how anti-HIV cytotoxic T lymphocytes can be activated and are useful for anti-HIV vaccine design.

Selon l'invention, des cellules dendritiques et des macrophages peuvent traiter des antig­nes extracellulaires pour une pr~sentation par des mol~cules MHC-I. Les ~pitopes VIH-1 d~riv~s de virions entrants sont pr~sent~s via la voie de transmission exog­ne de MHC-I dans des cellules dendritiques primaires humaines et, dans une moindre mesure, dans les macrophages, ce qui entra¹ne une activation cytotoxique des lymphocytes T en l'absence d'une n~osynth­se des prot~ines virales. La pr~sentation exog­ne d'antig­nes requiert des interactions virus-r~cepteur et une fusion des membranes virales et cellulaires qui soient ad~quates. Outre le fait qu'ils apportent de nouvelles connaissances concernant la mani­re dont les lymphocytes T cytotoxiques anti-HIV peuvent Útre activ~s, ces r~sultats sont utiles pour la conception d'un vaccin anti-VIH.

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