An endogenous HIV envelope-derived peptide without the terminal NH3+ group anchor is physiologically presented by major histocompatibility complex class I molecules.
Cytotoxic T lymphocytes (CTL) recognize viral peptidic antigens presented by major histocompatibility complex (MHC) class I molecules on the surface of infected cells. The CTL response is critical in clearance and prevention of HIV infection. Yet, there are no descriptions of physiological peptides derived from the viral envelope protein. In the few reports on endogenous MHC class I viral peptidic ligands from HIV internal proteins, definitive positive identification by mass spectrometry is lacking. The HIV-1 envelope glycoprotein gp160 induces a strong specific CTL response restricted by several human and murine MHC class I molecules, including H-2Dd. Previous analyses showed that this response can be optimally mimicked with the synthetic decameric peptide 318RGPGRAFVTI327. We aim to identify the endogenous natural peptides mediating the response to this epitope. Our data indicate the presence of, at least, two peptidic species of different length and sharing the same antigenic core, which are associated with the Dd presenting molecule in infected cells. One species is at least, probably, the optimal decapeptide. The second species, identified by mass spectrometry for the first time in HIV, is, unexpectedly, a nonamer, which lacks the correctly positioned N-terminal group to bind to Dd. And yet, it is present in similar amounts and, notably, is equally antigenic. Thus, the physiological set of HIV-derived MHC class I ligands is richer and different than expected from studies with synthetic peptides. This may help raise the plasticity and thus the effectiveness of the immune response against the viral infection. These data have implications for HIV vaccine development.
Centro Nacional de Microbiología. Instituto de Salud Carlos III, E-28220 Madrid, Spain.
Yolanda
Y
Samino
Daniel
D
Lopez
Sara
S
Guil
Patricia
P
de León
Margarita
M
Del Val
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D006023:Glycoproteins / Q000737:chemistry; D006678:HIV / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000378:metabolism; D014616:Vaccinia virus / Q000378:metabolism
D016207:Cytokines; D000939:Epitopes; D006023:Glycoproteins; D019302:HIV Envelope Protein gp160; D008024:Ligands; D010455:Peptides