N-glycosylation of HIV-gp120 may constrain recognition by T lymphocytes.
The HIV envelope protein gp120 is heavily glycosylated, having 55% of its molecular mass contributed by N-linked carbohydrates. We investigated the role of N-glycosylation in presentation of HIV-gp120 to T cells. T cell clones obtained from humans immunized with a recombinant nonglycosylated form of HIV-gp120 (env 2-3) were studied for their ability to recognize both env 2-3 and glycosylated gp120. We found that 20% of CD4+ T cell clones specific for env 2-3 fail to respond to glycosylated gp120 of the same HIV isolate. Using synthetic peptides, we mapped one of the epitopes recognized by such clones to the sequence 292-300 (NESVAINCT), which contains two asparagines that are glycosylated in the native gp120. These findings suggest that N-linked carbohydrates within an epitope can function as hindering structures that limit Ag recognition by T lymphocytes.
Botarelli
P
P
Department of Allergy/Immunology, Ciba-Geigy Ltd, Basel, Switzerland.
Houlden
B A
BA
Haigwood
N L
NL
Servis
C
C
Montagna
D
D
Abrignani
S
S
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D006023:Glycoproteins / Q000276:immunology*; D006031:Glycosylation; D015488:HIV Antigens / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000276:immunology; D013329:Structure-Activity Relationship
D000939:Epitopes; D006023:Glycoproteins; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins