HIV envelope protein inhibits MHC class I presentation of a cytomegalovirus protective epitope.

CTL recognize peptides that derive from viral protein Ags by proteolytic processing and are presented by MHC class I molecules. In this study we tested whether coexpression of viral Ags in the same cell leads to competition between them. To this end, two L(d)-restricted epitopes derived from HIV-1 e...

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Detalles Bibliográficos
Autores: Lopez, Daniel, Samino, Y, Koszinowski, U H, Val, Margarita del
Tipo de recurso: artículo
Fecha de publicación:2001
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/10777
Acceso en línea:http://hdl.handle.net/20.500.12105/10777
Access Level:acceso abierto
Palabra clave:Antigen Presentation
Animals
HIV Envelope Protein gp120
HIV Envelope Protein gp160
HIV-1
Histocompatibility Antigens Class I
Immediate-Early Proteins
Mice
Mice, Inbred BALB C
Peptide Fragments
Point Mutation
Descripción
Sumario:CTL recognize peptides that derive from viral protein Ags by proteolytic processing and are presented by MHC class I molecules. In this study we tested whether coexpression of viral Ags in the same cell leads to competition between them. To this end, two L(d)-restricted epitopes derived from HIV-1 envelope gp160 (ENV) and from CMV pp89 phosphoprotein were coexpressed. HIV ENV strain IIIB, but not MN variant, impaired recognition by specific CTL of CMV pp89 epitope 9pp89. Susceptibility to inhibition after ENV coexpression was inversely related to the amount of antigenic 9pp89 peptide processed from different antigenic constructs. In line with it, competition decreased the yield of naturally processed antigenic 9pp89 peptide bound to MHC class I molecules in coinfected cells. Also, point mutants of the presenting MHC class I molecule differed in their competition pattern. Collectively, the data imply that competition operates at the step of MHC-peptide complex assembly or stabilization. We conclude that, although not the rule, in certain combinations there is interference between different Ags expressed in the same cell and presented by the same MHC class I allele. These studies have implications for vaccine development and for understanding immunodominance.